Affinage

CD22

B-cell receptor CD22 · UniProt P20273

Length
847 aa
Mass
95.3 kDa
Annotated
2026-04-28
100 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD22 (Siglec-2) is a B-cell-restricted inhibitory co-receptor and α2,6-sialic acid-binding lectin that sets the threshold for B cell antigen receptor (BCR) signaling and contributes to peripheral B cell tolerance. Upon BCR ligation, CD22 is tyrosine-phosphorylated by Lyn kinase and recruits the phosphatase SHP-1 via its cytoplasmic ITIM motifs, suppressing calcium mobilization, MAP kinase activation, and downstream proliferative responses; CD22-deficient mice exhibit B cell hyperresponsiveness, expanded B-1 cells, and spontaneous autoantibody production (PMID:8864124, PMID:7542197, PMID:9252120, PMID:10209047). CD22's lectin domain engages α2,6-sialylated glycans in cis—predominantly on neighboring CD22 molecules forming homomultimeric nanoclusters—to regulate its proximity to the BCR, while trans interactions with sialylated ligands such as surface IgM on apposing B cells, sialylated antigens, and soluble IgM provide additional inhibitory feedback (PMID:16408005, PMID:20172905, PMID:23836650, PMID:19202057). Beyond BCR regulation, CD22 dampens TLR signaling through SOCS1/3 induction, promotes B cell gut homing via a sialic acid-dependent CD22–SHP-1–integrin β7 axis, and on aged microglia functions as an anti-phagocytic receptor whose blockade restores clearance of neurotoxic substrates and improves cognition (PMID:21178327, PMID:33589816, PMID:30944478).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1990 Medium

    CD22 was initially identified as a B-cell adhesion molecule related to MAG, establishing it within the immunoglobulin superfamily but leaving its signaling function unknown.

    Evidence Transfection and adhesion assays with CD22-expressing cells

    PMID:1691828

    Open questions at the time
    • Adhesion mechanism not linked to any signaling pathway
    • Ligand identity unknown
    • No in vivo validation
  2. 1993 High

    Identification of CD22 as an α2,6-sialic acid-binding lectin and demonstration of its physical association with the BCR complex established the molecular framework for its dual lectin–signaling receptor identity.

    Evidence CD22-Ig fusion binding assays with enzymatic validation; reciprocal co-immunoprecipitation of CD22 with sIgM/IgD/IgG, Igα, Igβ, and PTK72 from B cell lines

    PMID:7684686 PMID:8463234 PMID:8475064

    Open questions at the time
    • No downstream signaling effector identified
    • Unclear whether lectin activity is required for BCR association
  3. 1995 High

    Discovery that tyrosine-phosphorylated CD22 recruits SHP-1 after BCR cross-linking identified the core phosphatase effector of CD22 inhibitory signaling, while constitutive internalization to lysosomes revealed an additional layer of CD22 surface regulation.

    Evidence Phosphorylation-dependent co-IP of SHP-1 with CD22; flow cytometry and neuraminidase protection assays for endocytic trafficking

    PMID:7542197 PMID:7722303

    Open questions at the time
    • Specific tyrosine residues mediating SHP-1 binding not mapped
    • Functional consequence of SHP-1 recruitment not demonstrated in vivo
  4. 1996 High

    CD22 knockout mice revealed that CD22 is a physiological negative regulator of BCR signaling, resolving ambiguity about whether CD22 was activating or inhibitory in B cells.

    Evidence Gene-targeted CD22-deficient mice with calcium flux, proliferation, B-1 cell expansion, and serum autoantibody measurements

    PMID:8864124 PMID:9016707

    Open questions at the time
    • Relative contributions of lectin vs. ITIM domains not separated
    • Mechanism of autoantibody development not defined
  5. 1999 High

    Biochemical mapping of CD22–SHP-1 interaction showed that both SH2 domains of SHP-1 engage multiple phosphotyrosines on CD22, while aging CD22-KO mice developed high-affinity anti-dsDNA autoantibodies, linking CD22 loss to lupus-like autoimmunity.

    Evidence Phosphopeptide binding with mutagenesis of CD22 cytoplasmic tyrosines and SHP-1 SH2 domains; serum ELISA and somatic mutation analysis in CD22-KO mice

    PMID:10209047 PMID:9890995

    Open questions at the time
    • In vivo disease relevance to human autoimmunity not established
    • No structural basis for SHP-1–CD22 interaction
  6. 2002 High

    Knock-in and mutagenesis studies demonstrated that CD22's sialic acid-binding activity is required for its negative regulatory function, linking the lectin and signaling activities mechanistically.

    Evidence Reconstitution of CD22 ligand-binding mutants in CD22-/- B cells with calcium flux and SHP-1 co-IP readouts; SPR measurement of CD22–CD45 affinity (Kd ~130 μM)

    PMID:11994425 PMID:12115612

    Open questions at the time
    • Identity of physiological cis ligands unresolved
    • Contribution of trans vs. cis interactions unclear
  7. 2004 High

    Gene-targeted mice expressing ligand-binding-deficient CD22 separated lectin-dependent functions (surface expression, MZ B cell maintenance, proliferation) from lectin-independent ones (calcium inhibition, SHP-1 recruitment, migration), revealing that CD22 negative signaling does not absolutely require ligand binding.

    Evidence Knock-in mice with mutated CD22 sialic acid-binding domain, flow cytometry, calcium flux, B cell migration

    PMID:15378059

    Open questions at the time
    • Apparent contradiction with earlier mutagenesis results awaited resolution
    • Mechanism of ligand-independent ITIM signaling unclear
  8. 2005 High

    In situ photocross-linking revealed that CD22 homomultimers—not CD45 or other glycoproteins—are the dominant cis ligands, while genetic epistasis in ST6Gal1/CD22 double-KO mice showed that α2,6-sialylation controls BCR microdomain partitioning.

    Evidence Photoaffinity cross-linking proteomics on intact B cells; double-KO mice with membrane fractionation

    PMID:16369536 PMID:16408005

    Open questions at the time
    • Structural basis for homomultimer formation unknown
    • How microdomain redistribution translates to signaling quantitatively unclear
  9. 2010 High

    Identification of surface IgM on apposing B cells as the major trans ligand of CD22, and demonstration that CD22 dampens TLR signaling via SOCS1/3, expanded CD22's regulatory scope beyond BCR to innate-like pathways.

    Evidence UV photocross-linking proteomics and mass spectrometry for trans ligand identification; CD22-KO mice with TLR stimulation and SOCS expression analysis plus CD22 reconstitution

    PMID:20172905 PMID:21178327

    Open questions at the time
    • Molecular mechanism linking CD22 to SOCS induction not defined
    • Whether trans IgM engagement is inhibitory or activating in physiological contexts unclear
  10. 2013 High

    Dual knock-in mice separating CD22 ligand-binding from ITIM function resolved earlier contradictions: cis-ligand binding controls CD22–BCR proximity and calcium signaling magnitude, while ITIMs are essential for B cell survival, establishing a two-domain regulatory model.

    Evidence Knock-in mice with mutated CD22 ligand-binding domain or ITIMs, calcium flux and B cell turnover assays

    PMID:23836650

    Open questions at the time
    • Quantitative relationship between nanocluster size and signaling output not established
    • Role of CD22 in germinal center selection not fully addressed
  11. 2015 High

    Super-resolution imaging and computational modeling revealed that CD22 nanoclusters are highly mobile, providing 'global BCR surveillance' through rapid lateral diffusion regulated by CD45 and the lectin domain, explaining how low-abundance CD22 can inhibit dispersed BCR clusters.

    Evidence Super-resolution microscopy, single-particle tracking, Brownian dynamics simulations in wild-type, CD45-deficient, and lectin-mutant B cells

    PMID:26671981

    Open questions at the time
    • Whether nanocluster dynamics change during B cell activation not tested
    • No measurement of CD22–BCR encounter kinetics in live cells during antigen stimulation
  12. 2017 High

    The 2.1 Å crystal structure of CD22 revealed a preformed β-hairpin unique among Siglecs that dictates α2,6-sialic acid specificity and showed an extended ectodomain compatible with simultaneous nanocluster and trans engagement.

    Evidence X-ray crystallography of CD22 alone and CD22–epratuzumab complex

    PMID:28970495

    Open questions at the time
    • No structure of CD22 in complex with natural glycan ligand at atomic resolution
    • Ectodomain flexibility in membrane context unknown
  13. 2019 High

    A CRISPR screen in microglia identified CD22 as an anti-phagocytic receptor outside the B cell lineage; CD22 blockade in aged mice restored microglial clearance of neurotoxic substrates and improved cognition, redefining CD22 as a broader immune checkpoint.

    Evidence Genome-wide CRISPR-Cas9 screen, in vivo anti-CD22 antibody treatment, phagocytosis assays, RNA-seq, cognitive behavioral testing in aged mice

    PMID:30944478

    Open questions at the time
    • Downstream signaling pathway in microglia not fully characterized
    • Whether SHP-1 mediates anti-phagocytic function in microglia not shown
  14. 2021 High

    Two new functional axes were defined: CD22 associates with integrin β7 in a sialic acid-dependent manner to recruit SHP-1 and promote gut homing; separately, soluble CD22 binds IGF2R on myeloid cells to disrupt lysosomal trafficking, expanding CD22's roles beyond classical BCR regulation.

    Evidence Co-IP and knock-in mice with in vivo homing assays (β7 axis); unbiased proteomic screen identifying IGF2R, domain truncation, iPSC-derived microglia functional rescue

    PMID:33589816 PMID:34851695

    Open questions at the time
    • Whether sCD22–IGF2R interaction is relevant in vivo in aging or neurodegeneration not shown
    • Mechanism by which CD22 inhibits β7 endocytosis molecularly unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how CD22 nanocluster dynamics are regulated during germinal center responses, whether CD22's microglial anti-phagocytic function operates through SHP-1, the structural basis of the CD22–integrin β7 and sCD22–IGF2R interactions, and how CD22 loss contributes to human autoimmune disease.
  • No structural model of CD22 with natural glycan or integrin β7 partner
  • SHP-1 requirement in microglial CD22 signaling not tested
  • Human genetic evidence linking CD22 mutations to autoimmune disease lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 1 GO:0005764 lysosome 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5
Partners
AP2M1CD45IGF2RIGMITGB7LYNSHP-1
Complex memberships
BCR complex (low stoichiometry association)

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 CD22 mediates monocyte and erythrocyte adhesion and has a structure closely related to myelin-associated glycoprotein (MAG), a neuronal adhesion protein, identifying it as a B-cell adhesion receptor. Transfection and adhesion assays Nature Medium 1691828
1993 CD22 is a sialic acid-binding lectin that recognizes sialic acids in α2,6 linkage on N-linked oligosaccharides of multiple sialoglycoproteins including CD45, establishing CD22 as a member of a novel subset of Ig superfamily adhesion molecules. CD22-Ig fusion protein binding assays, periodate oxidation, sialyltransferase transfection in COS cells The Journal of Biological Chemistry High 8463234
1993 CD22 associates specifically with the B cell antigen receptor (BCR) complex including IgM, IgD, and IgG isotypes, in a low stoichiometry but stable association, and is rapidly tyrosine phosphorylated after antigen receptor cross-linking. In vitro kinase assay, co-immunoprecipitation from Burkitt lymphoma lines and tonsil cells European Journal of Immunology Medium 7684686
1993 CD22 co-immunoprecipitates with the sIgM-BCR complex along with Igα/mb-1, Igβ/B29, and PTK72, and becomes rapidly and strikingly tyrosine phosphorylated after sIgM cross-linking; CD22 contains the ARHI (antigen recognition homology I) motif present in other antigen receptor molecules. Co-immunoprecipitation in digitonin, immunoblot, in vitro kinase assay Proceedings of the National Academy of Sciences of the United States of America Medium 8475064
1992 CD22 directly interacts with multiple isoforms of CD45, and cross-linking of CD3 and CD22 ligands blocks anti-CD3-induced intracellular calcium increase and inhibits tyrosine phosphorylation of phospholipase Cγ1 in T cells, suggesting CD22-CD45 engagement modulates lymphocyte signaling. Direct binding assay with soluble CD22, calcium flux measurement, tyrosine phosphorylation assay Proceedings of the National Academy of Sciences of the United States of America Medium 1438211
1995 Tyrosine-phosphorylated CD22 recruits the tyrosine phosphatase SHP-1 (PTP1C) in a phosphorylation-dependent manner after BCR cross-linking, identifying SHP-1 as a downstream effector of CD22 signaling. Co-immunoprecipitation after anti-Ig stimulation, identification of 60-kDa associated protein as PTP1C European Journal of Immunology High 7542197
1995 CD22 is constitutively internalized by unstimulated B cells and degraded in an acidic intracellular compartment (lysosomes) without detectable recycling to the cell surface; anti-CD22 mAb ligation markedly increases internalization rate. Flow cytometry, neuraminidase protection and neuraminidase shift assays Journal of Immunology Medium 7722303
1995 Engagement of CD45 by soluble CD22 modulates early T cell signals in antigen receptor/CD3-mediated stimulation; addition of α2,6-sialic acid to the CD22 molecule itself abrogates CD22-ligand interactions. Soluble CD22-Ig fusion protein, T cell calcium flux, chimeric CD45 constructs, sialyltransferase treatment Proceedings of the National Academy of Sciences of the United States of America Medium 7537381
1996 CD22-deficient mice show hyperresponsive B cells with heightened calcium fluxes and cell proliferation at lower ligand concentrations, an expanded peritoneal B-1 cell population, and increased serum autoantibody titers, establishing CD22 as a negative regulator of antigen receptor signaling. Gene-targeted knockout mice, calcium flux measurement, proliferation assays, serum antibody titers Science High 8864124
1997 CD22-deficient mice show increased Ca2+ influx and lower survival of B cells upon BCR cross-linking, impaired T-cell independent immune responses, and absence of recirculating B cells from bone marrow, confirming CD22 as a negative regulator that sets the BCR signaling threshold. Targeted gene inactivation (knockout mice), calcium flux, B cell subset analysis, immune response assays Current Biology High 9016707
1997 CD19 and CD22 have counterregulatory effects on MAP kinase (ERK2, JNK, p38) activation by membrane immunoglobulin: CD19 co-ligation synergistically amplifies MAP kinase activation, while CD22 cross-linking to mIg suppresses it; sequestration of CD22 from mIg enhances MAP kinase activation. Co-ligation experiments, MAP kinase activation assays (ERK2, JNK, p38) Immunity Medium 9252120
1999 Multiple tyrosine residues within the cytoplasmic domain of CD22 interact with both SH2 domains of SHP-1; a minimum of two CD22 tyrosines are required for SHP-1 association, and both SH2 domains of SHP-1 are necessary for efficient binding. Phosphopeptide binding assays, mutational analysis of CD22 cytoplasmic domain tyrosines, SHP-1 domain analysis The Journal of Biological Chemistry High 9890995
1999 CD22 deficiency leads to development of high-affinity, somatically mutated, multiclonal IgG anti-dsDNA autoantibodies in aging mice, demonstrating that a single B-cell-specific gene defect is sufficient to trigger autoantibody development. CD22-deficient mice, serum antibody ELISA, affinity measurement, somatic mutation analysis The Journal of Experimental Medicine High 10209047
1999 CD22 ligation activates JNK/SAPK but not ERK2 signaling independently of BCR, and induces downregulation of Bcl-xL and Mcl-1, providing a mechanism for CD22-mediated apoptosis in B cells. Kinase activity assays (ERK2, JNK), AP-1/c-jun nuclear extract analysis, Bcl-2 family protein immunoblotting, B cell apoptosis assays Blood Medium 10438726
1999 CD45 positively regulates CD22 tyrosine phosphorylation; cross-linking of CD45 causes physical sequestration from CD22 leading to increased CD22 tyrosine phosphorylation and enhanced SHP-1 recruitment; CD45-deficient B cells show elevated basal CD22 phosphorylation and SHP-1 association. Co-immunoprecipitation, calcium flux assays, CD45-deficient B cell line, expression of catalytically inactive SHP-1 Journal of Immunology Medium 10228003
2002 Sialic acid binding domains of CD22 are required for CD22 to function as a negative regulator; CD22 mutants lacking sialic acid binding activity show reduced tyrosine phosphorylation and SHP-1 association, and greater Ca2+ responses after BCR stimulation. Site-directed mutagenesis of CD22 sialic acid binding domains, expression in CD22-/- B cell line, calcium flux assays, phosphorylation and co-immunoprecipitation The Journal of Experimental Medicine High 11994425
2002 CD22 binds native CD45 with low affinity (Kd ~130 μM) and very fast kinetics via enthalpically driven lectin-carbohydrate interaction; CD22 does not preferentially bind CD45 over other α2,6-sialylated glycoproteins in terms of intrinsic affinity. Surface plasmon resonance, thermodynamic (Van't Hoff) analysis European Journal of Immunology High 12115612
2003 CD22 interacts with AP50 (medium chain of the AP-2 clathrin adaptor complex) via tyrosine-based internalization motifs in its cytoplasmic domain; Tyr843 is the primary binding site for AP50, and either Tyr843 or Tyr863 is sufficient for mAb-mediated internalization. Yeast two-hybrid analysis, co-immunoprecipitation of α-adaptin, transfectant Jurkat cell internalization assays with wild-type and mutant CD22 Journal of Immunology High 12646615
2004 CD22 ligand binding regulates cell surface CD22 expression, IgM and MHC class II levels, marginal zone B cell maintenance, optimal BCR-induced proliferation, and B cell turnover; however, CD22 negative regulation of calcium mobilization, CD22 phosphorylation, SHP-1 recruitment, and B cell migration do not require CD22 ligand engagement. Gene-targeted mice expressing ligand-binding-deficient CD22 mutant, flow cytometry, calcium flux, B cell migration assays, co-immunoprecipitation Nature Immunology High 15378059
2005 CD22 forms homomultimeric complexes on B cell surfaces by recognizing glycans of neighboring CD22 molecules as cis ligands; CD45, sIgM, and other glycoproteins that bind CD22 in vitro are not important cis ligands in situ. In situ photoaffinity cross-linking of glycan ligands to CD22, immunoprecipitation Nature Chemical Biology High 16408005
2005 Ablation of CD22 in ST6Gal1-deficient mice (lacking the enzyme that generates α2-6-linked sialic acid CD22 ligands) restores BCR signaling; loss of CD22 ligand causes redistribution of BCR to clathrin-rich microdomains containing CD22, linking CD22-ligand interactions to BCR microdomain regulation. Double knockout mice (Cd22-/- St6gal1-/-), BCR signaling assays, membrane fractionation/microdomain analysis Nature Immunology High 16369536
2006 Anti-CD22 mAbs that block CD22 ligand binding accelerate mature B cell turnover 2-4 fold and inhibit survival of normal and malignant B cells in vivo; effects are independent of complement and FcRs and absent in CD22AA mice expressing ligand-binding-deficient CD22. In vivo mAb treatment, B cell turnover assays, adoptive transfer of normal and malignant B cells, CD22AA knock-in mice Journal of Immunology High 16920943
2007 Human B lymphocytes express α2-6-sialylated 6-sulfo-N-acetyllactosamine as a preferred high-affinity ligand for CD22; CD22 binding to B cells was abrogated by sulfate metabolism inhibition and by anti-sulfated LacNAc antibody. Cell binding assays, NaClO3 inhibition, monoclonal antibody blocking, flow cytometry The Journal of Biological Chemistry Medium 17728258
2009 Sialylated multivalent antigens engage CD22 in trans and inhibit key steps in BCR signaling, revealing that antigens bearing CD22 ligands can suppress B cell activation through trans CD22 interactions. Sialylated multivalent antigen synthesis, calcium flux assays, BCR signaling readouts Proceedings of the National Academy of Sciences of the United States of America Medium 19202057
2009 The Lyn-CD22-SHP-1 inhibitory pathway becomes operational as B cells mature; Lyn deficiency substantially enhances mature but not immature B cell BCR signaling in a manner similar to CD22 deficiency, indicating this pathway is critical for peripheral B cell tolerance. Lyn-deficient and CD22-deficient mice, calcium flux and ERK MAPK assays at different B cell developmental stages Journal of Immunology Medium 19380785
2010 IVIg sialic acid-bearing glycans bind CD22 on B cells, reducing BCR-mediated tyrosine phosphorylation of Lyn and BLNK, upregulating PLCγ2 activation, sustaining ERK1/2 activation, and arresting cell cycle at G1, linking CD22's lectin function to IVIg immunomodulation. Confocal microscopy of sialylated vs. desialylated IgG binding to CD22, signaling pathway analysis by immunoblot, cell cycle analysis Blood Medium 20516366
2010 IgM on apposing B cells is the major in situ trans ligand of CD22; UV photocross-linking of CD22 to glycoproteins on apposing B cells identified IgM as selectively redistributed to the cell contact site. UV photocross-linking proteomics, mass spectrometry-based quantitative proteomics, immunochemical analysis of cross-linked products Molecular & Cellular Proteomics High 20172905
2010 CD22 negatively regulates TLR3, TLR4, and TLR9 signaling in B cells, at least in part by promoting induction of SOCS1 and SOCS3 (suppressors of cytokine signaling); CD22 expression in a CD22-/- B cell line blunts TLR ligand responses and inhibits LPS-induced NF-κB transcription. CD22-deficient mice, TLR ligand stimulation assays, SOCS1/3 expression analysis, NF-κB reporter assay, CD22 reconstitution in CD22-/- cell line Journal of Innate Immunity Medium 21178327
2011 CD22 serves as a receptor for soluble IgM (sIgM) due to α2,6-linked sialic acid glycans on sIgM; antigen-sIgM complexes activate CD22 in trans, creating a negative feedback loop for B cell activation analogous to FcγRIIB. CD22-deficient mice, sIgM binding assays, BCR signaling analysis European Journal of Immunology Medium 21956693
2013 Liposomal nanoparticles displaying both antigen and glycan ligands of CD22 (STALs) induce antigen-specific B cell apoptosis through a tolerogenic program; this mechanism requires CD22 engagement and induces robust antigen-specific tolerance to protein antigens in mice. Liposomal nanoparticle synthesis, in vitro B cell apoptosis assays with mouse and human B cells, in vivo tolerance induction in mice, FVIII hemophilia model The Journal of Clinical Investigation High 23722906
2013 CD22 cis-ligand binding controls CD22 association to the BCR and is crucial for negative regulation of Ca2+ signaling; mice with mutated CD22 ligand-binding domain show strongly reduced Ca2+ signaling, while mice with mutated CD22 ITIMs show increased Ca2+ responses, increased B cell turnover, and impaired B cell survival. Knock-in mice with mutated CD22 ligand-binding domain or mutated ITIMs, calcium flux assays, B cell turnover analysis Proceedings of the National Academy of Sciences of the United States of America High 23836650
2015 CD22 is organized into nanodomains and is highly mobile on naïve B cells; its lateral diffusion and nanoscale organization are regulated by CD45 and its lectin domain; mathematical modeling and experiments suggest CD22 provides 'global BCR surveillance' through fast diffusion to maintain inhibitory function despite low numbers of molecules. Super-resolution microscopy, single-particle tracking, Brownian dynamics simulations, CD45-deficient and CD22 lectin-domain mutant B cells The EMBO Journal High 26671981
2015 On germinal center (GC) B cells, loss of high-affinity CD22 ligands unmasks the CD22 binding site relative to naïve B cells, promoting trans ligand recognition; in humans, 6-O-sulfate on GlcNAc is lost on GC B cells; in mice, Neu5Gc is replaced by Neu5Ac on GC B cells. Glycan binding assays, flow cytometry, mass spectrometry of glycan structures on B cell subsets The Journal of Biological Chemistry Medium 26507663
2017 Crystal structure of human CD22 at 2.1 Å resolution reveals that α2-6 sialic acid ligand specificity is dictated by a preformed β-hairpin unique among Siglecs; the CD22 ectodomain adopts an extended conformation enabling simultaneous nanocluster formation and trans ligand binding; N-linked glycosylation is critical for epratuzumab engagement at domain 3. X-ray crystallography (2.1 Å for CD22 alone, 3.1 Å for CD22-epratuzumab complex), structure-function validation Nature Communications High 28970495
2019 CD22 is upregulated on aged microglia, mediates the anti-phagocytic effect of α2,6-linked sialic acid, and its inhibition promotes clearance of myelin debris, amyloid-β oligomers, and α-synuclein fibrils; long-term CNS CD22 antibody blockade reprograms microglia towards a homeostatic transcriptional state and improves cognitive function in aged mice. CRISPR-Cas9 knockout screens, RNA sequencing, in vivo antibody blockade, phagocytosis assays, cognitive behavior testing Nature High 30944478
2021 CD22 associates with integrin β7 on B cell surfaces in a sialic acid-dependent manner, recruiting Shp1 to β7 and inhibiting β7 endocytosis, thereby enhancing surface α4β7 display and B cell homing to gut-associated lymphoid tissue; this CD22-Shp1 axis requires both the CD22 sialic acid-binding and Shp1-binding domains. Co-immunoprecipitation, CD22 KO mice, knock-in mice with mutated CD22 Shp1-binding or carbohydrate-binding domains, β7 endocytosis assays, in vivo homing assays Nature Immunology High 33589816
2021 Soluble CD22 (sCD22) binds to insulin-like growth factor 2 receptor (IGF2R) on human myeloid cells near mannose 6-phosphate-binding domains, disrupting lysosomal protein trafficking; CD22 blocking antibodies ameliorate lysosome dysfunction in NPC1 mutant iPSC-derived microglia-like cells. Unbiased genetic and proteomic screens, IGF2R truncation experiments, iPSC-derived microglia functional assays, CD22 blocking antibody treatment Science Translational Medicine High 34851695
2023 Notch1 signaling in regulatory T cells (Tregs) induces CD22 expression, leading to Treg destabilization in an mTORC1-dependent manner and promotion of systemic inflammation in MIS-C patients; dominant-negative mutations in Notch1 regulators NUMB/NUMBL cause Notch1 upregulation and downstream CD22 induction. Genetic analysis of MIS-C patients, Notch1 signaling pathway analysis in Tregs, mTORC1 pathway assessment The Journal of Clinical Investigation Medium 36282598

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nature medicine 495 34312556
2012 Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood 488 23243285
1996 Hyperresponsive B cells in CD22-deficient mice. Science (New York, N.Y.) 409 8864124
2019 CD22 blockade restores homeostatic microglial phagocytosis in ageing brains. Nature 360 30944478
1997 CD22 is a negative regulator of B-cell receptor signalling. Current biology : CB 351 9016707
1997 CD22, a B lymphocyte-specific adhesion molecule that regulates antigen receptor signaling. Annual review of immunology 245 9143697
1999 Deficiency in CD22, a B cell-specific inhibitory receptor, is sufficient to predispose to development of high affinity autoantibodies. The Journal of experimental medicine 238 10209047
2021 CRISPR/Cas9-Engineered Universal CD19/CD22 Dual-Targeted CAR-T Cell Therapy for Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 229 33627493
2005 Homomultimeric complexes of CD22 in B cells revealed by protein-glycan cross-linking. Nature chemical biology 229 16408005
2018 Preclinical Development of Bivalent Chimeric Antigen Receptors Targeting Both CD19 and CD22. Molecular therapy oncolytics 225 30581986
1993 CD22, a B cell-specific immunoglobulin superfamily member, is a sialic acid-binding lectin. The Journal of biological chemistry 200 8463234
2013 Antigenic liposomes displaying CD22 ligands induce antigen-specific B cell apoptosis. The Journal of clinical investigation 194 23722906
2019 CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia. Leukemia 191 31110217
1990 The B-cell antigen CD22 mediates monocyte and erythrocyte adhesion. Nature 181 1691828
1993 CD22 associates with the human surface IgM-B-cell antigen receptor complex. Proceedings of the National Academy of Sciences of the United States of America 180 8475064
2011 Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clinical cancer research : an official journal of the American Association for Cancer Research 179 22003067
2018 CD22: A Regulator of Innate and Adaptive B Cell Responses and Autoimmunity. Frontiers in immunology 163 30323814
1989 The reliability of cytoplasmic CD3 and CD22 antigen expression in the immunodiagnosis of acute leukemia: a study of 500 cases. Leukemia 163 2465463
2021 Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells. Nature medicine 155 33888899
1993 Association of CD22 with the B cell antigen receptor. European journal of immunology 150 7684686
2005 The role of CD22 and other inhibitory co-receptors in B-cell activation. Current opinion in immunology 146 15886119
2005 CD22: a multifunctional receptor that regulates B lymphocyte survival and signal transduction. Advances in immunology 143 16227086
2015 Characterization of CD22 expression in acute lymphoblastic leukemia. Pediatric blood & cancer 142 25728039
2004 CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms. Nature immunology 129 15378059
2017 Molecular basis of human CD22 function and therapeutic targeting. Nature communications 127 28970495
2005 Ablation of CD22 in ligand-deficient mice restores B cell receptor signaling. Nature immunology 126 16369536
2008 Targeting CD22 reprograms B-cells and reverses autoimmune diabetes. Diabetes 123 18689692
2021 Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models. Science translational medicine 122 33762438
2010 IVIg modulates BCR signaling through CD22 and promotes apoptosis in mature human B lymphocytes. Blood 121 20516366
2009 CD22 and Siglec-G: B-cell inhibitory receptors with distinct functions. Immunological reviews 120 19594633
2009 Sialylated multivalent antigens engage CD22 in trans and inhibit B cell activation. Proceedings of the National Academy of Sciences of the United States of America 109 19202057
2021 Combination of CD19 and CD22 CAR-T cell therapy in relapsed B-cell acute lymphoblastic leukemia after allogeneic transplantation. American journal of hematology 107 33725422
1995 Phosphotyrosine-dependent association between CD22 and protein tyrosine phosphatase 1C. European journal of immunology 105 7542197
1988 Role of the CD22 human B cell antigen in B cell triggering by anti-immunoglobulin. Journal of immunology (Baltimore, Md. : 1950) 104 3257985
1992 CD22-mediated stimulation of T cells regulates T-cell receptor/CD3-induced signaling. Proceedings of the National Academy of Sciences of the United States of America 103 1438211
1995 Constitutive endocytosis and degradation of CD22 by human B cells. Journal of immunology (Baltimore, Md. : 1950) 97 7722303
1997 Counterregulation by the coreceptors CD19 and CD22 of MAP kinase activation by membrane immunoglobulin. Immunity 95 9252120
1995 Construction and characterization of a humanized, internalizing, B-cell (CD22)-specific, leukemia/lymphoma antibody, LL2. Molecular immunology 95 8643111
2013 CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling. Proceedings of the National Academy of Sciences of the United States of America 91 23836650
2015 Nanoscale organization and dynamics of the siglec CD22 cooperate with the cytoskeleton in restraining BCR signalling. The EMBO journal 89 26671981
2002 Sialic acid binding domains of CD22 are required for negative regulation of B cell receptor signaling. The Journal of experimental medicine 87 11994425
1995 Regulation of CD45 engagement by the B-cell receptor CD22. Proceedings of the National Academy of Sciences of the United States of America 82 7537381
1998 CD22 negatively and positively regulates signal transduction through the B lymphocyte antigen receptor. Seminars in immunology 75 9695185
2007 Preclinical and clinical evaluation of epratuzumab (anti-CD22 IgG) in B-cell malignancies. Oncogene 72 17530024
2021 CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma. Blood 69 33512414
2010 Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus. Arthritis research & therapy 69 21050432
1999 CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade. Blood 69 10438726
2009 Developmental acquisition of the Lyn-CD22-SHP-1 inhibitory pathway promotes B cell tolerance. Journal of immunology (Baltimore, Md. : 1950) 67 19380785
2020 Glycoengineering of NK Cells with Glycan Ligands of CD22 and Selectins for B-Cell Lymphoma Therapy. Angewandte Chemie (International ed. in English) 65 33314603
2013 Targeting CD22 in B-cell malignancies: current status and clinical outlook. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 64 23696252
2004 Molecular interactions regulate BCR signal inhibition by CD22 and CD72. Trends in immunology 64 15364057
2001 CD19, CD21, and CD22: multifaceted response regulators of B lymphocyte signal transduction. International reviews of immunology 64 11913948
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