Affinage

FCER2

Low affinity immunoglobulin epsilon Fc receptor · UniProt P06734

Length
321 aa
Mass
36.5 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD23 (FcεRII/FCER2) is a type II transmembrane C-type lectin that serves as the low-affinity IgE receptor, functioning as a central regulator of IgE homeostasis, IgE-dependent antigen transport across epithelial barriers, and B-cell activation. Its C-type lectin head domain binds IgE in a calcium-independent manner at sites spanning both the head and stalk regions, while simultaneously engaging CD21 at a distinct site to co-regulate IgE synthesis; the oligomerization state of soluble CD23 fragments released by ADAM10 (and context-dependently by ADAM8 or MMP9) determines whether IgE production is stimulated (trimeric sCD23 via CD21/mIgE co-capping) or inhibited (monomeric sCD23) (PMID:16172256, PMID:27343203, PMID:17389606, PMID:22393152). On epithelial cells, the CD23a isoform mediates bidirectional transcytosis of IgE and IgE–allergen immune complexes — diverting them from lysosomal degradation — to initiate subepithelial mast cell degranulation and allergic inflammation in both gut and airway, a process dependent on isoform-specific intracytoplasmic sorting signals that direct clathrin-dependent endocytosis and basolateral targeting (PMID:16831589, PMID:15843555, PMID:25783969). On B cells, membrane CD23 negatively regulates BCR signaling by restraining actin-dependent BCR clustering and downstream Btk/WASp phosphorylation, signals through Fyn kinase and the IKKβ–NF-κB pathway upon cross-linking, and facilitates CD23-dependent antigen capture for MHC class II presentation to T cells; its transcription is positively driven by EBNA-2/Notch2–CBF1, IL-4, IgE itself, and NFATc1 (the latter tonically suppressed by JNK1), and negatively regulated by Egr-1 (PMID:27181049, PMID:10490984, PMID:16034084, PMID:11986231, PMID:28112734).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1988 Medium

    Mapping the CD23-binding epitope on IgE to a 10-amino-acid stretch in the Cε3 domain (CH3, residues 367–376) provided the first molecular definition of the IgE–CD23 interface.

    Evidence Monoclonal antibody epitope mapping with overlapping peptides and CD23 competition binding

    PMID:2459242

    Open questions at the time
    • Peptide-level mapping only; no structural data on the CD23 contact residues
    • Does not address the contribution of the CD23 stalk to IgE binding
  2. 1991 Medium

    Two foundational discoveries established CD23 as a signaling receptor and a transcriptional target: cross-linking CD23 activates the Src-family kinase Fyn and induces IL-2R expression, while EBNA-2 transactivates the CD23a promoter through a 186-bp cis-element, linking EBV infection to CD23 upregulation.

    Evidence Co-IP of Fyn with CD23 in transfected YT cells plus cross-linking assay; CD23 promoter-reporter deletional analysis in EBV-negative B-lymphoma cells

    PMID:1649318 PMID:1717997

    Open questions at the time
    • Fyn association shown by single co-IP without reciprocal validation
    • Signaling downstream of Fyn not mapped
    • EBNA-2 mechanism of action on CD23 promoter (direct DNA binding vs. adaptor) not resolved
  3. 1992 High

    Identification of CD21 as a direct ligand of CD23 that enhances IL-4-induced IgE production established the CD23–CD21 axis as a key regulatory circuit for IgE synthesis on B cells.

    Evidence Fluorescent liposome binding with recombinant CD23, CD21-transfected cells, anti-CD21/anti-CD23 blocking antibodies, functional IgE assay

    PMID:1386409

    Open questions at the time
    • Stoichiometry of CD23–CD21 complex unknown
    • Whether CD23–CD21 interaction occurs in cis or in trans on FDCs not resolved
  4. 1997 Medium

    Demonstrating that Egr-1 overexpression represses CD23 transcription in B cells identified the first negative transcriptional regulator and linked BCR activation to CD23 downregulation.

    Evidence Egr-1 cDNA transfection into murine K46 and human Ramos B cells, flow cytometry

    PMID:9300687

    Open questions at the time
    • Direct binding of Egr-1 to the CD23 promoter not demonstrated
    • Single gain-of-function approach without loss-of-function confirmation
  5. 1998 High

    Two parallel advances defined the shedding mechanism and an in vivo feedback loop: biochemical characterization showed CD23 is cleaved by a ~63-kDa membrane metalloprotease, while IgE-deficient mice revealed that IgE itself positively regulates surface CD23 levels, establishing a ligand-receptor positive feedback circuit.

    Evidence Membrane fractionation and inhibitor profiling of CD23 sheddase activity; IgE−/− mouse with in vivo IgE infusion rescue

    PMID:9677315 PMID:9786437

    Open questions at the time
    • The ~63-kDa protease was not molecularly identified at this stage
    • Mechanism of IgE-mediated CD23 stabilization (transcriptional vs. post-translational) not distinguished
  6. 1999 High

    CD23 cross-linking activates the IKKβ–NF-κB pathway via upstream tyrosine kinase activity, and soluble CD23 binds αv integrins/CD47 to trigger proinflammatory cytokine release, revealing two distinct CD23 signaling modalities — membrane-proximal NF-κB activation and soluble CD23-mediated integrin signaling.

    Evidence Dominant-negative IKKβ/IκBα, kinase assays, EMSA in U937 cells; sCD23 binding to αv/β3/CD47 transfectants with blocking antibodies and cytokine ELISA

    PMID:10037797 PMID:10490984

    Open questions at the time
    • The upstream tyrosine kinase connecting CD23 to IKKβ is unidentified
    • Physiological relevance of integrin-mediated sCD23 signaling in vivo not confirmed
  7. 2000 High

    Demonstrating that epithelial CD23 mediates IgE-dependent transcytosis of luminal antigen across intestinal enterocytes in sensitized rats established CD23 as a transepithelial antigen shuttle driving allergic inflammation.

    Evidence Sensitized rat model, immunogold EM co-localization, anti-CD23 blocking in Ussing chambers

    PMID:11018076

    Open questions at the time
    • Directionality and kinetics of transcytosis not fully characterized
    • Isoform specificity (CD23a vs. CD23b) not addressed in this system
  8. 2001 High

    CD23 on follicular dendritic cells suppresses IgE responses via a non-lymphoid radioresistant cell compartment, and CD23 forms a surface complex with HLA-DR that recycles through antigen-loading compartments, linking CD23 to MHC class II antigen presentation.

    Evidence Reciprocal adoptive transfers in CD23-Tg mice with FDC co-culture; co-IP of CD23 with HLA-DR and confocal trafficking in B cells

    PMID:11290762 PMID:11454061

    Open questions at the time
    • Whether CD23–HLA-DR association is direct or adaptor-mediated is unclear
    • FDC-mediated suppression mechanism (competitive trapping vs. signaling) not resolved
  9. 2002 High

    Identification of Notch2/CBF1 as a transcriptional activator complex at the CD23a promoter connected CD23 regulation to the Notch signaling pathway and explained EBNA-2-driven CD23 upregulation through shared CBF1 binding sites.

    Evidence EMSA/supershift with Notch2 antibody, activated Notch2 transfection inducing endogenous CD23a in pre-B cells

    PMID:11986231

    Open questions at the time
    • Whether Notch1 or other Notch paralogs also regulate CD23 not tested
    • Chromatin-level confirmation (ChIP) absent
  10. 2003 High

    ADAM8, ADAM15, and ADAM28 were identified as CD23 sheddases, and mouse enterocytes were shown to express a CD23b splice variant (Δ5) with distinct internalization properties, resolving both the protease identity and isoform-specific trafficking in epithelial transcytosis.

    Evidence Synthetic peptide screening, co-IP of ADAM8 with CD23, active-site mutant; RT-PCR of enterocyte RNA, CD23−/− mouse transport assay

    PMID:12637252 PMID:12777399

    Open questions at the time
    • Relative contributions of ADAM8/15/28 vs. ADAM10 in physiological shedding unresolved
    • Human enterocyte isoform repertoire not fully mapped at this point
  11. 2005 High

    NMR structure of the CD23 lectin domain revealed calcium-independent self-trimerization and simultaneous but spatially distinct binding sites for IgE and CD21, while mutagenesis of CD23a/b intracytoplasmic exons defined the sorting signals governing isoform-specific endocytosis, basolateral targeting, and plasma membrane retention.

    Evidence NMR chemical shift perturbation mapping; exon-swap mutagenesis in polarized MDCK cells, endocytosis/recycling assays; adoptive transfer of CD23+ B cells into CD23−/− mice demonstrating IgE-mediated antigen presentation

    PMID:15843555 PMID:16034084 PMID:16172256

    Open questions at the time
    • Full atomic structure of the CD23 trimer in complex with IgE not available at this stage
    • Whether simultaneous CD21+IgE binding occurs on the intact trimer vs. monomer unclear
  12. 2006 High

    Showing that only the CD23a isoform (not CD23b) mediates bidirectional IgE transcytosis in primary human intestinal epithelial cells, diverting allergen–IgE complexes from degradation to trigger subepithelial mast cell degranulation, provided the definitive isoform-specific mechanism for epithelial allergic inflammation.

    Evidence Retroviral transduction of CD23a or CD23b into polarized T84 cells, transcytosis assay, RBL degranulation assay

    PMID:16831589

    Open questions at the time
    • Mechanism by which CD23a avoids lysosomal routing not molecularly defined
    • Whether lipid raft association contributes to isoform-specific sorting unknown
  13. 2007 High

    ADAM10 was established as the primary physiological CD23 sheddase cleaving at two stalk sites, and the oligomerization state of the resulting soluble fragments was shown to be the key determinant of IgE regulation: monomeric sCD23 inhibits while trimeric sCD23 stimulates IgE synthesis; additionally, epithelial CD23 cross-linking by IgE–allergen complexes activates ERK/JNK–AP-1 to induce CCL20/IL-8 and dendritic cell recruitment.

    Evidence siRNA, dominant-negative ADAM10, specific inhibitors, peptide cleavage assays; recombinant monomeric vs. oligomeric sCD23 in B cell IgE assays; CD23 shRNA knockdown in Caco-2 cells with phospho-signaling

    PMID:17389606 PMID:17576766 PMID:18054562

    Open questions at the time
    • How ADAM10 access to CD23 stalk is regulated in vivo not known
    • Whether CCL20 release occurs in vivo in human airway epithelium not confirmed
  14. 2009 High

    TLR4 stimulation by LPS induces CD23 upregulation and MMP9-dependent sCD23 release specifically from transitional B cells, revealing an innate-immune trigger for CD23 shedding distinct from ADAM10.

    Evidence MMP9 knockout mice, qRT-PCR, flow cytometry, ELISA, in vivo and in vitro LPS treatment

    PMID:19635918

    Open questions at the time
    • Whether MMP9 cleaves CD23 at the same stalk sites as ADAM10 is unknown
    • Relative physiological importance of MMP9 vs. ADAM10 shedding in innate responses not quantified
  15. 2012 High

    Trimeric sCD23 stimulates IgE by co-capping mIgE and CD21 on B cell membranes, whereas monomeric sCD23 inhibits IgE, mechanistically explaining the oligomerization-dependent switch; separately, CD23 was identified as a receptor for the cytokine AIMP1/p43, triggering ERK1/2-dependent TNF-α release.

    Evidence Recombinant defined sCD23 oligomers with ADAM10 inhibitor uncoupling, capping assay; receptor screen of 499 targets, siRNA knockdown, ELISA

    PMID:22393152 PMID:22767513

    Open questions at the time
    • Structural basis of mIgE/CD21 co-capping by trimeric sCD23 unknown
    • AIMP1–CD23 interaction awaits independent replication and in vivo validation
  16. 2013 Medium

    β2-adrenergic signaling on primed B cells upregulates CD23 and ADAM10 co-localization on exosomes via PKA/p38 MAPK; transfer of these exosomes to recipient B cells enhances IgE production, revealing an intercellular amplification loop.

    Evidence β2AR agonist treatment, exosome isolation/EM, PKA/p38 inhibitors, β2AR-KO B cells, ELISPOT

    PMID:24140643

    Open questions at the time
    • Whether exosomal CD23/ADAM10 transfer occurs in vivo not demonstrated
    • Mechanism by which exosome-delivered CD23 enhances IgE in recipient cells not defined
  17. 2014 High

    P2X7 receptor activation by extracellular ATP was identified as a rapid trigger of ADAM10-mediated CD23 shedding from B cells, linking danger-signal sensing to acute regulation of surface CD23 levels.

    Evidence P2X7 KO mice, P2X7 antagonist, ADAM10-specific inhibitor, flow cytometry, ELISA

    PMID:25155463

    Open questions at the time
    • Downstream signaling between P2X7 and ADAM10 activation not mapped
    • In vivo relevance during infection or tissue damage not shown
  18. 2015 High

    Bone marrow chimera experiments demonstrated that CD23 on radioresistant airway epithelial cells is required for transepithelial allergen–IgE transport and the full allergic airway inflammatory response in vivo, including eosinophilia, collagen deposition, and airway hyperreactivity.

    Evidence CD23 KO mice, bone marrow chimeras, OVA challenge, airway function, histology, anti-CD23 antibody inhalation

    PMID:25783969

    Open questions at the time
    • Whether CD23 transcytosis in airway epithelium is apical-to-basal, basal-to-apical, or bidirectional in vivo not fully resolved
  19. 2016 High

    CD23 negatively regulates BCR signaling by limiting actin-dependent BCR clustering, Btk and WASp phosphorylation, and cell spreading upon encounter with membrane-associated antigen; separately, the CD23 stalk was identified as a second IgE-binding site, and non-glycosylated monomeric CD23 was shown to bind IgE more effectively than glycosylated forms.

    Evidence CD23 KO mouse B cells on antigen-presenting surfaces, confocal/flow/phospho-Western; recombinant CD23 structural variants with glycosylation-site mutations, EM, binding assays

    PMID:27181049 PMID:27343203

    Open questions at the time
    • Molecular mechanism by which CD23 restrains actin polymerization and BCR clustering unknown
    • Structural basis of stalk–IgE interaction not resolved at atomic level
  20. 2017 High

    Crystal structure of CD23–IgE-Fc revealed asymmetric binding with two lectin heads engaging IgE-Fc at markedly different affinities due to IgE conformational asymmetry; JNK1 was shown to suppress CD23 expression by inhibiting NFATc1 at the CD23 promoter, with JNK1 deficiency enhancing CD23-dependent antifungal immunity via nitric oxide production.

    Evidence X-ray crystallography and ITC; JNK1 KO mice with C. albicans infection, promoter reporter assays, CD23 blockade epistasis, human cell pharmacological validation

    PMID:28112734 PMID:28361904

    Open questions at the time
    • Full trimeric CD23–intact IgE complex structure unavailable
    • Whether JNK1–NFATc1–CD23 axis operates in human B cells in vivo not confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of trimeric CD23 simultaneously engaging IgE and CD21 in the context of IgE regulation; the molecular mechanism by which membrane CD23 restrains BCR clustering/actin dynamics; the intracellular trafficking pathway by which CD23a avoids lysosomal degradation during transcytosis; and the relative in vivo contributions of ADAM10, ADAM8, and MMP9 to CD23 shedding across different immune contexts.
  • No full-length trimeric CD23–IgE–CD21 ternary complex structure
  • Mechanism linking CD23 to actin/BCR clustering restraint uncharacterized
  • CD23a lysosomal avoidance pathway not molecularly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 7 GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 7 GO:0005886 plasma membrane 7 GO:0005768 endosome 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-162582 Signal Transduction 5 R-HSA-74160 Gene expression (Transcription) 4
Partners
ADAM10ADAM8AIMP1CD47CR2FYNITGAVMMP9
Complex memberships
CD23–CD21 complexCD23–HLA-DR complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CD23 (FcεRII) directly binds CD21 (complement receptor 2) on B cells and follicular dendritic cells; this CD23–CD21 interaction specifically increases IL-4-induced IgE production from blood mononuclear cells, establishing CD21 as a functional ligand of CD23 that participates in IgE regulation. Fluorescent liposome-binding assay with recombinant CD23, CD21-transfected cell lines, inhibition by anti-CD21/anti-CD23 monoclonal antibodies, Western blot, and functional IgE production assay Nature High 1386409
2005 The NMR solution structure of the CD23 C-type lectin domain reveals that CD23 self-associates into a trimer, binds IgE and CD21 at distinct sites on the lectin head, and can bind both ligands simultaneously; none of these interactions require calcium despite the C-type lectin fold. IgE and CD23 can also form high-molecular-mass multimeric complexes. NMR spectroscopy, concentration-dependent chemical shift perturbation mapping, ligand-induced chemical shift analysis The Journal of experimental medicine High 16172256
2017 Crystal structure of a CD23/IgE-Fc complex shows that two lectin-like head domains of CD23 bind IgE-Fc with affinities differing by more than an order of magnitude, with only one head domain bound to one of the two identical IgE heavy chains in the asymmetrically bent IgE-Fc, revealing asymmetric binding. X-ray crystallography, isothermal titration calorimetry Scientific reports High 28361904
2003 ADAM8, ADAM15, and ADAM28 (MDC-L) catalyze ectodomain shedding of CD23; ADAM8-dependent sCD23 release requires proteolytically active ADAM8, which physically associates with membrane-bound CD23, and this release is inhibited by hydroxamic acid metalloprotease inhibitors. Synthetic peptide substrate library screening, in vitro ectodomain shedding assay, co-immunoprecipitation of ADAM8 with CD23, metalloprotease inhibitor treatment The Journal of biological chemistry High 12777399
2007 ADAM10 is the primary metalloprotease responsible for cleaving CD23 at two distinct stalk sites to release soluble CD23 (sCD23); tissue inhibitors of metalloproteinases, a prodomain-based ADAM10 inhibitor, dominant-negative ADAM10, and siRNA knockdown of ADAM10 all partially inhibit sCD23 release and cause accumulation of membrane CD23. Peptide cleavage assays, ADAM10 dominant-negative construct expression, siRNA knockdown, ADAM10-specific inhibitor treatment, ELISA for sCD23 The Journal of biological chemistry High 17389606
1998 CD23 is cleaved from the cell surface by an integral membrane metalloprotease of ~63 kDa; this activity is inhibited by metalloprotease inhibitors (1,10-phenanthroline, imidazole, batimastat) but not by serine, cysteine, or acid protease inhibitors, and the same or similar activity is present in fibroblasts and monocytic cell lines not expressing CD23. Plasma membrane fractionation, gel-filtration chromatography, neo-epitope antibody cleavage assay, pharmacological inhibitor panel The Biochemical journal High 9677315
2012 Soluble CD23 monomers (derCD23 and exCD23) inhibit IgE synthesis in human B cells, whereas trimeric/oligomeric soluble CD23 (lzCD23) stimulates IgE synthesis; trimeric sCD23 binds cells co-expressing mIgE and mCD21 and caps these proteins on the B cell membrane, indicating that oligomerization state determines the functional outcome of sCD23 on IgE regulation. Recombinant protein production, human B cell IL-4/anti-CD40 IgE synthesis assay, ADAM10 inhibitor (GI254023X) to uncouple cleavage from sCD23 effects, siRNA knockdown, cell-surface capping assay Journal of immunology (Baltimore, Md. : 1950) High 22393152
2007 Soluble CD23 monomers inhibit and oligomers stimulate IgE synthesis in human B cells after heavy-chain class switching; three defined fragments (monomeric derCD23, monomeric exCD23, oligomeric lzCD23) were characterized biochemically to establish this structure–activity relationship. Recombinant fragment preparation, B cell IgE synthesis assay The Journal of biological chemistry High 17576766
1991 CD23/FcεRII is physically associated with the Src-family tyrosine kinase p59Fyn (but not p56Lck); cross-linking of CD23 in CD23-transfected YT cells activates IL-2 receptor (p55/Tac) expression, indicating that CD23 delivers activation signals via Fyn kinase. cDNA transfection of YT cells, anti-FcεRII crosslinking, co-immunoprecipitation with anti-Fyn antibody, IL-2 receptor induction assay Proceedings of the National Academy of Sciences of the United States of America Medium 1717997
1999 Cross-linking of CD23 in monocytic U937 cells activates IKKβ, which phosphorylates IκBα at Ser32/Ser36, leading to IκBα degradation and NF-κB activation; this pathway requires upstream tyrosine kinase activity. A dominant-negative IκBα(S32A/S36A) or dominant-negative IKKβ completely blocks CD23-induced NF-κB activation and gene transcription. Dominant-negative IκBα and IKKβ overexpression, co-transfection assays, IKK activity assays, NF-κB EMSA, phosphospecific IκBα immunoblotting Journal of immunology (Baltimore, Md. : 1950) High 10490984
2000 CD23 expressed on intestinal epithelial cells mediates IgE-dependent transcytosis of antigen (HRP) across enterocytes in sensitized rats; anti-CD23 antibody applied luminally inhibits both antigen transport and the hypersensitivity reaction, and sensitization induces CD23 expression on enterocytes. Active sensitization rat model, immunohistochemistry for CD23, immunogold EM co-localization of CD23 and antigen in endosomes, serum transfer, anti-CD23 blocking antibody in Ussing chamber The Journal of clinical investigation High 11018076
2006 CD23a isoform (but not CD23b) is constitutively expressed by primary human intestinal epithelial cells and acts as a bidirectional transporter of IgE; CD23a diverts allergen-IgE complexes away from lysosomal degradation and delivers them transcellularly, enabling degranulation of mast cells below the epithelial barrier. RT-PCR of primary IECs, retroviral transfection of polarized T84 cells with CD23a or CD23b, transcytosis assay, RBL degranulation assay Gastroenterology High 16831589
2003 Mouse intestinal enterocytes express only the CD23b isoform; a novel alternative splice variant CD23b-Δ5 (lacking exon 5) mediates constitutive internalization and uptake of free IgE or anti-CD23, whereas classic CD23b is less efficiently internalized but transports IgE/allergen complexes; CD23-deficient mice lack enhanced transepithelial antigen transport. RT-PCR and sequencing of enterocyte RNA, CD23-/- mouse intestinal transport assay, exon-specific functional comparison American journal of physiology. Gastrointestinal and liver physiology High 12637252
2005 CD23a undergoes constitutive clathrin-dependent endocytosis directed by an internalization signal in its CD23a-specific intracytoplasmic exon, which also serves as a basolateral targeting signal in polarized epithelial cells; CD23b is stable at the plasma membrane due to a negative regulatory signal in its CD23b-specific intracellular exon. Mutagenesis of intracellular exons, transfection into MDCK polarized cells, endocytosis/recycling assays in multiple cell lines Journal of immunology (Baltimore, Md. : 1950) High 15843555
2001 CD23 forms a non-covalent complex with HLA-DR (MHC class II) on the surface of human B cells; following endocytosis triggered by an IgE-antigen complex or anti-HLA-DR antibody, the HLA-DR–CD23 complex recycles to the cell surface via compartments resembling peptide-loading compartments, on a time scale consistent with antigen presentation. Surface labeling and intracellular trafficking of RPMI 8866 B cells, co-immunoprecipitation of CD23 with HLA-DR, confocal microscopy of endosomal routing Immunology Medium 11454061
1999 Soluble CD23 binds directly to the αv integrin subunit and the vitronectin receptor (αvβ3); co-expression of CD47 augments sCD23 binding; the vitronectin receptor/CD47 complex mediates sCD23-induced proinflammatory TNF-α, IL-12, and IFN-γ release from monocytes. Binding assays on αv+β3+ cell lines with/without CD47, purified αv protein binding, CHO single-chain transfectant binding, cytokine release inhibition by anti-CD47, anti-β3, and anti-αv monoclonal antibodies The Journal of cell biology Medium 10037797
2009 TLR4 ligation by LPS induces transcriptional upregulation of CD23 and generation of soluble CD23 from B cells; this shedding requires matrix metalloprotease 9 (MMP9), as MMP9-deficient B cells fail to release sCD23 in response to LPS. Type 1 transitional B cells uniquely produce MMP9 upon LPS stimulation. MMP9 knockout mice, quantitative RT-PCR, flow cytometry, ELISA for sCD23, in vitro and in vivo LPS treatment of murine and human B cells Journal of immunology (Baltimore, Md. : 1950) High 19635918
2014 P2X7 receptor activation by extracellular ATP induces rapid shedding of CD23 from primary human and murine B cells via ADAM10; this process is blocked by the P2X7 antagonist AZ10606120, is absent in P2X7 knockout mouse B cells, and is inhibited by the ADAM10 antagonist GI254023X and the broad metalloprotease inhibitor BB-94. P2X7 knockout mice, P2X7-specific antagonist, ADAM10-specific inhibitor, broad metalloprotease inhibitor, flow cytometry, ELISA Immunology and cell biology High 25155463
2016 CD23 negatively regulates B-cell receptor (BCR) signaling: CD23 knockout B cells show increased cell spreading area, BCR clustering, phosphotyrosine levels, Btk phosphorylation, F-actin accumulation, and phospho-WASp in the contact zone upon stimulation with membrane-associated antigen. CD23 knockout mice, membrane antigen presentation assay, flow cytometry, confocal microscopy, phospho-Western blotting Scientific reports High 27181049
2016 The stalk region of CD23 contains a previously unrecognized IgE-binding site; non-N-glycosylated monomeric CD23 shows superior IgE binding compared with glycosylated CD23; the therapeutic anti-IgE antibody omalizumab blocks IgE binding to both FcεRI and CD23. Expression of four CD23 variants (full extracellular, N-glycosylation site mutant, complete head, truncated head), gel filtration, circular dichroism, binding and inhibition assays, negative-stain electron microscopy The Journal of allergy and clinical immunology High 27343203
2015 Epithelial CD23 on airway epithelial cells transcytoses IgE and OVA-IgE immune complexes across the airway epithelial barrier in vivo; CD23 knockout mice or chimeric mice lacking CD23 on radioresistant airway structural/epithelial cells have significantly reduced allergic airway inflammation, eosinophilia, collagen deposition, and airway hyperreactivity after OVA challenge. CD23 knockout mice, bone-marrow chimera experiments, in vivo OVA sensitization/challenge, airway hyperreactivity measurement, histology, CD23-blocking antibody inhalation Mucosal immunology High 25783969
2011 CD23-dependent transcytosis of IgE and IgE-immune complexes occurs across polarized human airway epithelial (Calu-3) cells and primary human airway epithelial monolayers; IL-4 upregulates CD23 expression and enhances transcytosis; anti-CD23 antibody or soluble CD23 competitively reduces transcytosis efficiency; transcytosed IgE-antigen complexes retain biological activity to induce mast cell degranulation. Transcytosis assay in polarized Calu-3 monolayers, primary human airway epithelial cells, IL-4 stimulation, CD23-blocking antibody/soluble CD23, human mast cell degranulation assay Journal of immunology (Baltimore, Md. : 1950) High 21307287
2007 CD23 cross-linking on human intestinal epithelial Caco-2 cells by IgE-allergen complexes activates ERK and JNK MAP kinases and AP-1, triggering upregulation and release of CCL20 and IL-8; silencing CD23 expression with shRNA abrogates this response; secreted CCL20 induces dendritic cell migration. IgE-antigen complex stimulation of Caco-2, RT-PCR and ELISA for CCL20/IL-8, phospho-Western blotting (ERK, JNK, p38, NF-κB), stable CD23 shRNA knockdown, dendritic cell migration assay Gastroenterology High 18054562
2012 CD23 is identified as a functional receptor for the proinflammatory cytokine AIMP1/p43; AIMP1 binds CD23 with high affinity (identified in a screen of 499 soluble receptors), CD23 knockdown attenuates AIMP1-induced TNF-α secretion from THP-1 and PBMCs, and AIMP1-induced TNF-α release via CD23 involves ERK1/2 activation. Screen of 499 soluble receptors, AIMP1 binding to CD23 confirmed by pull-down, CD23 siRNA knockdown, ERK1/2 phosphorylation assay, cytokine ELISA Journal of cell science Medium 22767513
2013 β2-adrenergic receptor engagement on IL-4/CD40L-primed murine B cells increases CD23 and ADAM10 protein expression and promotes their co-localization on exosomes in a PKA- and p38 MAPK-dependent manner; transfer of these exosomes to recipient primed B cells increases IgE production per cell. β2AR agonist treatment, ADAM10/CD23 Western blot, flow cytometry of exosomes, electron microscopy, PKA and p38 MAPK inhibitors, ELISPOT for IgE, β2AR-deficient B cells as controls Journal of immunology (Baltimore, Md. : 1950) Medium 24140643
2002 Notch2 intracellular domain (NotchIC) is a component of a transcription factor complex (C1) that binds CBF1-recognition sites in the CD23a core promoter; EBV infection and activated Notch2 drive CD23a transcription; transfection of activated Notch2 into REH pre-B cells induces endogenous CD23a expression, identifying CD23a as a Notch2/CBF1 target gene. EMSA with CBF1-site probes, supershift assays with Notch2 antibody, transient transfection of activated Notch2, RT-PCR for endogenous CD23a, EBV-infected B cells as model Blood High 11986231
1991 EBNA-2 transactivates CD23a transcription through a 186-bp cis-acting element located at positions -275/-89 relative to the type a CD23 mRNA start site; this element confers EBNA-2 responsiveness to a heterologous promoter in either orientation and at variable distances, and type 1 EBNA-2 is more potent than type 2 EBNA-2 at activating this element. Transfection of CD23 promoter-reporter constructs with deletional analysis into EBV-negative B-lymphoma cells, heterologous promoter (HSV-TK) assays, Northern blot for mRNA Journal of virology High 1649318
1997 Egr-1 transcription factor overexpression in murine B cells (K46 line) and human Ramos B cells down-regulates CD23 and CD95 (Fas) expression, establishing CD23 as a transcriptional target repressed by Egr-1 following BCR activation. Egr-1 cDNA transfection into B cell lines, flow cytometry for CD23 and CD95, functional apoptosis assay with anti-CD95 Journal of immunology (Baltimore, Md. : 1950) Medium 9300687
1998 In vivo, IgE directly regulates CD23 expression on murine B cells: IgE-deficient mice have ~3-fold less surface CD23 despite normal B cell numbers; intravenous infusion of IgE into IgE-/- mice restores CD23 expression to wild-type levels, demonstrating a positive feedback loop whereby IgE ligand stabilizes/upregulates its own low-affinity receptor. IgE-deficient mouse model, flow cytometry for CD23, in vivo IgE infusion rescue experiment, in vitro IL-4/CD40L stimulation controls International immunology High 9786437
2001 Suppression of IgE responses in CD23-transgenic mice is mediated by radioresistant non-lymphoid cells, not by transgenic B or T cells: adoptive transfer of normal lymphocytes into transgenic mice still shows IgE suppression, whereas transgenic lymphocytes in normal hosts give normal IgE responses; follicular dendritic cells (FDC) expressing high CD23 are identified as candidate suppressors, as CD23-Tg FDCs inhibit IgE production by normal B cells in vitro. Adoptive transfer experiments (normal ↔ CD23-Tg bone marrow), B cell proliferation and IgE synthesis assays in vitro, germinal center histology, co-culture of Tg FDCs with normal B cells Journal of immunology (Baltimore, Md. : 1950) High 11290762
2005 IgE-mediated enhancement of antibody and T-cell responses in vivo requires CD23+ B cells: transfer of CD23+ B cells into CD23-deficient mice rescues the ability to respond to IgE-antigen; B cells can take up antigen via CD23 and present it to activate naïve T cells in vivo, leading to T-cell expansion and enhanced antibody responses. Adoptive transfer of CD23+ B cells into CD23-deficient mice, TCR-transgenic CD4+ T cell transfer, in vivo immunization with IgE-antigen, flow cytometry, splenic immunohistochemistry Journal of immunology (Baltimore, Md. : 1950) High 16034084
2017 JNK1 suppresses CD23 expression through negative regulation of NFATc1-mediated transcription at the CD23 gene promoter; JNK1-deficient mice upregulate CD23 and show enhanced antifungal immunity dependent on CD23-mediated nitric oxide production; pharmacological JNK inhibition recapitulates this antifungal effect in mouse and human cells. JNK1-deficient mice, C. albicans infection model, CD23 promoter reporter assays, NFATc1 transcription factor analysis, CD23 blockade experiment, NO production assay, JNK inhibitor treatment of mouse and human cells Nature medicine High 28112734
1988 A monoclonal antibody recognizing amino acids 367–376 (CH3 domain) of IgE inhibits IgE binding to CD23 (FcεRII), mapping the CD23-binding site on IgE to a 10-amino acid stretch near N-glycosylation site Asn-371 in the Cε3 domain; the antibody does not recognize a carbohydrate epitope as it binds E. coli-derived IgE peptides. Anti-IgE monoclonal antibody binding to recombinant overlapping peptides, heat-denatured IgE, competition binding assay with CD23 Journal of immunology (Baltimore, Md. : 1950) Medium 2459242

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 CD21 is a ligand for CD23 and regulates IgE production. Nature 433 1386409
1989 CD23: a multi-functional receptor/lymphokine? Immunology today 253 2525911
2000 DC-SIGN; a related gene, DC-SIGNR; and CD23 form a cluster on 19p13. Journal of immunology (Baltimore, Md. : 1950) 215 10975799
2003 Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23. The Journal of biological chemistry 147 12777399
2010 CD23/FcεRII: molecular multi-tasking. Clinical and experimental immunology 141 20831712
2002 Notch2 is involved in the overexpression of CD23 in B-cell chronic lymphocytic leukemia. Blood 115 11986231
2005 The structure of human CD23 and its interactions with IgE and CD21. The Journal of experimental medicine 112 16172256
1993 Human B cell precursors proliferate and express CD23 after CD40 ligation. The Journal of experimental medicine 111 7686210
1991 Epstein-Barr virus nuclear protein 2 transactivates a cis-acting CD23 DNA element. Journal of virology 109 1649318
2000 Enhanced intestinal transepithelial antigen transport in allergic rats is mediated by IgE and CD23 (FcepsilonRII). The Journal of clinical investigation 107 11018076
1994 Distinction between small lymphocytic and mantle cell lymphoma by immunoreactivity for CD23. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 87 8058704
2017 JNK1 negatively controls antifungal innate immunity by suppressing CD23 expression. Nature medicine 85 28112734
2015 Structure and dynamics of IgE-receptor interactions: FcεRI and CD23/FcεRII. Immunological reviews 84 26497523
1989 Modulation of IL-4-induced human IgE production in vitro by IFN-gamma and IL-5: the role of soluble CD23 (s-CD23). Journal of cellular biochemistry 82 2496134
2024 CD23+IgG1+ memory B cells are poised to switch to pathogenic IgE production in food allergy. Science translational medicine 79 38324641
1989 Expression and functional role of CD23 on T cells. European journal of immunology 79 2522048
1994 Soluble CD23 reliably reflects disease activity in B-cell chronic lymphocytic leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 76 7931486
1994 B-cell signalling via the C-type lectins CD23 and CD72. Immunology today 75 7945782
2007 The low affinity IgE receptor (CD23) is cleaved by the metalloproteinase ADAM10. The Journal of biological chemistry 74 17389606
2006 Transcytosis of IgE-antigen complexes by CD23a in human intestinal epithelial cells and its role in food allergy. Gastroenterology 74 16831589
2005 IgE enhances antibody and T cell responses in vivo via CD23+ B cells. Journal of immunology (Baltimore, Md. : 1950) 72 16034084
2000 Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated vasculitides. Clinical and experimental rheumatology 70 10949720
1999 Up-regulation of interleukin-4 and CD23/FcepsilonRII in minimal change nephrotic syndrome. Pediatric nephrology (Berlin, Germany) 69 10353405
2002 CD23 (the low-affinity IgE receptor) as a C-type lectin: a multidomain and multifunctional molecule. Cellular and molecular life sciences : CMLS 68 12022472
2021 The role of CD23 in the regulation of allergic responses. Allergy 67 33378583
2022 IgG memory B cells expressing IL4R and FCER2 are associated with atopic diseases. Allergy 66 36445014
1999 The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23. The Journal of cell biology 66 10037797
1992 CD23 antigen regulation and signaling in chronic lymphocytic leukemia. The Journal of clinical investigation 66 1532590
2019 Human Mesenchymal Stem Cell-Treated Regulatory CD23+CD43+ B Cells Alleviate Intestinal Inflammation. Theranostics 65 31367246
2005 Anti-CD23. Clinical reviews in allergy & immunology 65 16222084
1989 IgE receptor on human eosinophils (FcERII). Comparison with B cell CD23 and association with an adhesion molecule. Journal of immunology (Baltimore, Md. : 1950) 64 2531185
2007 Soluble CD23 monomers inhibit and oligomers stimulate IGE synthesis in human B cells. The Journal of biological chemistry 60 17576766
1999 High expression of CD23 in the proliferation centers of chronic lymphocytic leukemia in lymph nodes and spleen. Human pathology 60 10374772
1995 CD23 and B-cell activation. Current opinion in immunology 59 7546400
2000 CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness. American journal of respiratory and critical care medicine 58 10712348
1991 Fyn tyrosine kinase associated with Fc epsilon RII/CD23: possible multiple roles in lymphocyte activation. Proceedings of the National Academy of Sciences of the United States of America 58 1717997
2012 Soluble CD23 controls IgE synthesis and homeostasis in human B cells. Journal of immunology (Baltimore, Md. : 1950) 57 22393152
2003 Intestinal epithelial CD23 mediates enhanced antigen transport in allergy: evidence for novel splice forms. American journal of physiology. Gastrointestinal and liver physiology 57 12637252
2001 Endocytosis and recycling of the complex between CD23 and HLA-DR in human B cells. Immunology 56 11454061
2004 CD23 expression in mediastinal large B-cell lymphomas. Histopathology 55 15569053
2016 CD23 can negatively regulate B-cell receptor signaling. Scientific reports 52 27181049
2011 CD23-dependent transcytosis of IgE and immune complex across the polarized human respiratory epithelial cells. Journal of immunology (Baltimore, Md. : 1950) 52 21307287
2011 FCER2 T2206C variant associated with chronic symptoms and exacerbations in steroid-treated asthmatic children. Allergy 52 21958076
1999 Altered expression and action of the low-affinity IgE receptor FcepsilonRII (CD23) in asthmatic airway smooth muscle. The Journal of allergy and clinical immunology 52 10482830
1994 Transgene CD23 expression on lymphoid cells modulates IgE and IgG1 responses. Journal of immunology (Baltimore, Md. : 1950) 52 8089484
1997 Structure and functions of CD23. International reviews of immunology 50 9651788
2003 CD23 expression in mantle cell lymphoma: clinicopathologic features of 18 cases. American journal of clinical pathology 49 14608904
1990 Expression of CD23 antigen and its regulation by IL-4 in chronic lymphocytic leukemia. Leukemia research 49 2137545
2020 CD23 expression on switched memory B cells bridges T-B cell interaction in allergic rhinitis. Allergy 48 32198890
2011 CD23(+)/CD21(hi) B-cell translocation and ipsilateral lymph node collapse is associated with asymmetric arthritic flare in TNF-Tg mice. Arthritis research & therapy 47 21884592
1995 Regulation of IgE synthesis by CD23/CD21 interaction. International archives of allergy and immunology 47 7542093
2005 CD5, CD10, and CD23 expression in Waldenstrom's macroglobulinemia. Clinical lymphoma 45 15794857
2002 The clinical and diagnostic relevance of CD23 expression in the chronic lymphoproliferative disease. Cancer 45 11920534
1990 Allergen-directed expression of Fc receptors for IgE (CD23) on human T lymphocytes is modulated by interleukin 4 and interferon-gamma. European journal of immunology 44 2142456
1988 A monoclonal anti-IgE antibody against an epitope (amino acids 367-376) in the CH3 domain inhibits IgE binding to the low affinity IgE receptor (CD23). Journal of immunology (Baltimore, Md. : 1950) 43 2459242
1995 The two CD23 isoforms display differential regulation in chronic lymphocytic leukaemia. British journal of haematology 42 7873388
2015 Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of allergic airway inflammation. Mucosal immunology 41 25783969
2000 Early expression of iepsilon, CD23 (FcepsilonRII), IL-4Ralpha, and IgE in the human fetus. The Journal of allergy and clinical immunology 41 11080714
1997 Transcription factor Egr-1 activity down-regulates Fas and CD23 expression in B cells. Journal of immunology (Baltimore, Md. : 1950) 41 9300687
1991 Heterogeneous expression of CD23 epitopes by eosinophils from patients. Relationships with IgE-mediated functions. European journal of immunology 41 1717283
2007 Allergen-IgE complexes trigger CD23-dependent CCL20 release from human intestinal epithelial cells. Gastroenterology 40 18054562
1988 Functional interaction between B cell subpopulations defined by CD23 expression. European journal of immunology 39 2974422
2019 CD23 provides a noninflammatory pathway for IgE-allergen complexes. The Journal of allergy and clinical immunology 38 31437490
2000 Association study of the chromosomal region containing the FCER2 gene suggests it has a regulatory role in atopic disorders. American journal of respiratory and critical care medicine 36 10712310
2012 Monoclonal antibodies to equine CD23 identify the low-affinity receptor for IgE on subpopulations of IgM+ and IgG1+ B-cells in horses. Veterinary immunology and immunopathology 35 22405681
2009 Expression of CD27 and CD23 on peripheral blood B lymphocytes in humans of different ages. Blood transfusion = Trasfusione del sangue 34 19290077
1998 CD23 (FcepsilonRII) release from cell membranes is mediated by a membrane-bound metalloprotease. The Biochemical journal 34 9677315
2008 CD23+ mantle cell lymphoma: a clinical pathologic entity associated with superior outcome compared with CD23- disease. American journal of clinical pathology 33 18628084
2022 Bidirectional Transport of IgE by CD23 in the Inner Ear of Patients with Meniere's Disease. Journal of immunology (Baltimore, Md. : 1950) 32 35046106
2010 CD5+CD23+ leukemic cell populations in TCL1 transgenic mice show significantly increased proliferation and Akt phosphorylation. Leukemia 32 20357824
1992 Expression, regulation and function of human Fc epsilon RII (CD23) antigen. Immunologic research 32 1287120
2017 IgE binds asymmetrically to its B cell receptor CD23. Scientific reports 31 28361904
1991 Biology and chemistry of low affinity IgE receptor (Fc epsilon RII/CD23). Critical reviews in immunology 31 1834078
2015 High affinity targeting of CD23 inhibits IgE synthesis in human B cells. Immunity, inflammation and disease 30 26732048
2001 Suppression of IgE responses in CD23-transgenic animals is due to expression of CD23 on nonlymphoid cells. Journal of immunology (Baltimore, Md. : 1950) 30 11290762
1989 Regulation by interleukin 2 of CD23 expression of leukemic and normal B cells: comparison with interleukin 4. European journal of immunology 30 2526738
1995 Interleukin-4 and soluble CD23 serum levels in asthmatic atopic children. Journal of investigational allergology & clinical immunology 29 8574430
1998 Inhibitors of the p38 mitogen-activated kinase modulate IL-4 induction of low affinity IgE receptor (CD23) in human monocytes. Journal of immunology (Baltimore, Md. : 1950) 28 9834082
2006 Differential T cell-mediated regulation of CD23 (Fc epsilonRII) in B cells and follicular dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 27 16585575
1997 Function of CD23 in the response of human B cells to antigen. European journal of immunology 27 9045933
2000 Quantitative expression of CD23 and its ligand CD21 in chronic lymphocytic leukemia. Haematologica 26 11064465
1999 The signal transduction pathway of CD23 (Fc epsilon RIIb) targets I kappa B kinase. Journal of immunology (Baltimore, Md. : 1950) 26 10490984
1998 The expression of murine B cell CD23, in vivo, is regulated by its ligand, IgE. International immunology 25 9786437
2019 TNF-Induced Interstitial Lung Disease in a Murine Arthritis Model: Accumulation of Activated Monocytes, Conventional Dendritic Cells, and CD21+/CD23- B Cell Follicles Is Prevented with Anti-TNF Therapy. Journal of immunology (Baltimore, Md. : 1950) 24 31659014
2016 Critical and direct involvement of the CD23 stalk region in IgE binding. The Journal of allergy and clinical immunology 24 27343203
2014 Activation of the P2X7 receptor induces the rapid shedding of CD23 from human and murine B cells. Immunology and cell biology 24 25155463
1993 CD23 expression on B-lymphocytes and its modulation by cytokines in allergic patients. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 24 8221262
1993 Chromosomal location and isoform analysis of mouse Fc epsilon RII/CD23. Molecular immunology 24 8417372
2013 A role of FCER1A and FCER2 polymorphisms in IgE regulation. Allergy 23 24354852
2009 TLR4-mediated signaling induces MMP9-dependent cleavage of B cell surface CD23. Journal of immunology (Baltimore, Md. : 1950) 23 19635918
2007 IgE enhances specific antibody and T-cell responses in mice overexpressing CD23. Scandinavian journal of immunology 23 17635803
2022 Lenalidomide enhances CD23.CAR T cell therapy in chronic lymphocytic leukemia. Leukemia & lymphoma 22 35259043
2012 Identification of CD23 as a functional receptor for the proinflammatory cytokine AIMP1/p43. Journal of cell science 22 22767513
2013 Adrenergic regulation of IgE involves modulation of CD23 and ADAM10 expression on exosomes. Journal of immunology (Baltimore, Md. : 1950) 21 24140643
2008 The cut-off levels of CD23 expression in the differential diagnosis of MCL and CLL. Hematological oncology 21 18381689
2005 Intracellular trafficking of CD23: differential regulation in humans and mice by both extracellular and intracellular exons. Journal of immunology (Baltimore, Md. : 1950) 21 15843555
1999 Importance of CD23 for collagen-induced arthritis: delayed onset and reduced severity in CD23-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 21 10201957
1994 CD23 and IgE expression during the human immune response to cutaneous leishmaniasis: possible role in monocyte activation. Research in immunology 21 8008965
2006 Analysis of the regulatory role of BAFF in controlling the expression of CD21 and CD23. Molecular immunology 20 17140663
2008 Analysis of CD23 antigen expression in B-chronic lymphocytic leukaemia and its correlation with clinical parameters. Medical oncology (Northwood, London, England) 19 18183502