Affinage

FCGR2A

Low affinity immunoglobulin gamma Fc region receptor II-a · UniProt P12318

Length
317 aa
Mass
35.0 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FCGR2A (FcγRIIa/CD32A) is a low-affinity activating IgG Fc receptor expressed on myeloid cells, platelets, and endothelial cells that transduces immune complex signals to drive phagocytosis, platelet activation, dendritic cell maturation, and anaphylaxis. Its two extracellular Ig-like domains bind all four human IgG subclasses, with the second domain (D2) harboring critical contact residues including the H131/R131 polymorphism that governs allotype-dependent affinity — the H131 variant uniquely confers efficient IgG2 binding and generally higher affinity for IgG1 and IgG3 (PMID:7930727, PMID:20007585). Cross-linking triggers ITAM-dependent recruitment of Src-family kinases and Syk, activation of Btk/Tec kinases, PLCγ phosphorylation, and Ca²⁺ flux, while lipid-raft association regulates IgG-binding capacity and a cytoplasmic L-T-L motif routes calcium signals to phagosomes to enable phagolysosome fusion (PMID:7612894, PMID:19494328, PMID:12676989, PMID:31809536). Beyond classical ITAM signaling, FcγRIIa cooperates with FcRn as a coreceptor for IgG1 immune complex responses, delivers DNA-containing immune complexes to TLR9 in plasmacytoid dendritic cells, and on platelets is the critical receptor mediating IgG immune complex–driven thrombosis and IgG-dependent anaphylaxis (PMID:32658257, PMID:15668740, PMID:29654057, PMID:20585032).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1989 High

    Molecular cloning established FCGR2A as a gene encoding a distinct activating IgG receptor isoform with two Ig-like extracellular domains, a transmembrane segment, and a unique cytoplasmic tail, resolving the molecular identity of the CD32A isoform.

    Evidence cDNA cloning, sequencing, and transfection expression in heterologous cells

    PMID:2529342

    Open questions at the time
    • Full domain architecture and 3D structure not yet determined
    • Signaling mechanism of cytoplasmic tail unknown
  2. 1994 High

    Identification of the H131/R131 single-nucleotide polymorphism as the molecular basis for differential IgG subclass binding — particularly unique IgG2 recognition by the H131 variant — answered how genetic variation in a single receptor controls subclass-specific immunity and susceptibility to encapsulated bacterial infections.

    Evidence Genotyping by allele-specific oligonucleotides combined with phagocytosis assays of IgG2-opsonized bacteria in neutrophils from defined donors

    PMID:7930726 PMID:7930727 PMID:8046255

    Open questions at the time
    • Structural basis of how position 131 alters IgG2 contact not resolved
    • Clinical impact on infection outcomes required prospective studies
  3. 1995 High

    Domain mapping and mutagenesis pinpointed the IgG-binding interface to two segments in extracellular domain 2 (Ser109–Val116 and Ser130–Thr135) while showing domain 1 contributes to overall affinity, defining the ligand-recognition architecture at residue-level resolution.

    Evidence Chimeric FcγRII/FcεRIα receptors, site-directed mutagenesis, and IgG binding assays

    PMID:7673151 PMID:7679695

    Open questions at the time
    • Co-crystal structure with IgG Fc not yet available
    • Contribution of glycosylation to binding affinity unclear
  4. 1995 Medium

    Biochemical dissection of the signaling cascade revealed that FcγRIIa cross-linking activates Src-family kinases and Syk, leading to PLCγ phosphorylation, Shc recruitment, and Ca²⁺ flux — establishing the ITAM-dependent proximal signaling pathway distinct from the inhibitory FcγRIIb isoform.

    Evidence Kinase inhibitor studies, immunoprecipitation, Ca²⁺ measurements in transfected B cells and primary cells

    PMID:7612894 PMID:8283039

    Open questions at the time
    • Relative contribution of individual Src-family members not determined
    • Signaling requirement for phagocytosis vs. other effector functions not separated
  5. 2000 High

    Discovery that neutrophil activation (fMLP) converts surface FcγRIIa from a low- to high-affinity IgG-binding state without changing expression levels revealed an inside-out affinity regulation mechanism, explaining how resting cells avoid spurious immune complex engagement.

    Evidence IgG-opsonized erythrocyte rosetting with CD16B-deficient donor neutrophils vs. CHO cells expressing CD32A

    PMID:10648424

    Open questions at the time
    • Molecular mechanism of affinity switch (conformational change, lateral partner, or lipid environment) not defined
    • Whether affinity modulation operates in other cell types unknown
  6. 2003 High

    Identification of the cytoplasmic L-T-L motif as the element routing Ca²⁺ signals to nascent phagosomes and enabling phagolysosome fusion — independent of the ITAM — resolved how FcγRIIa couples ligand engagement to microbicidal phagosome maturation beyond simple internalization.

    Evidence Site-directed mutagenesis of L-T-L motif, high-speed Ca²⁺ imaging, lysosomal colocalization microscopy

    PMID:11719384 PMID:12676989

    Open questions at the time
    • Direct binding partner of the L-T-L motif not identified
    • Whether L-T-L motif regulates Ca²⁺ channel recruitment or release from stores unclear
  7. 2005 High

    Demonstration that FcγRIIa internalizes DNA-containing immune complexes into TLR9-positive endosomal compartments of plasmacytoid dendritic cells established a cooperative FcγRIIa–TLR9 pathway linking adaptive IgG responses to innate nucleic acid sensing, with direct relevance to lupus pathogenesis.

    Evidence Sorting of CD32+ vs. CD32− PDCs, colocalization microscopy, anti-CD32 blocking, cytokine production assays

    PMID:15668740

    Open questions at the time
    • Whether other FcγRs can substitute for CD32A in this pathway not tested
    • Mechanism of immune complex routing to TLR9-containing compartment not defined
  8. 2009 High

    Mutagenesis and cholesterol manipulation showed that lipid-raft association regulates FcγRIIa IgG-binding capacity — with raft-excluded mutants binding less IgG and GPI-anchored (constitutively raft-associated) CD32A binding more — providing a membrane-organizational mechanism for affinity modulation.

    Evidence A224S and C241A mutants, GPI-anchored CD32A, cholesterol depletion/sequestration, IgG binding assays

    PMID:19494328

    Open questions at the time
    • Relationship between raft association and inside-out activation (fMLP effect) not integrated
    • Whether raft partitioning changes receptor oligomerization state unknown
  9. 2009 High

    Quantitative 2D affinity measurements extended the allotype-dependent binding hierarchy to all tested IgG subclasses — H131 outcompetes R131 for IgG1, IgG2, and IgG3 — refining the functional impact of the polymorphism beyond the IgG2-centric view.

    Evidence Ig fusion proteins of both CD32A alleles, competition binding and 2D affinity assays

    PMID:20007585

    Open questions at the time
    • Absolute 3D KD values for each allotype–subclass pair not all determined
    • Functional consequences for IgG4 binding by each allotype not measured
  10. 2010 High

    In vivo demonstration that FcγRIIa on platelets is necessary and sufficient for immune complex–induced thrombosis — using transgenic mice, aglycosylated antibody controls, and thrombin inhibition — established the receptor as the key mediator of antibody-triggered thrombotic events such as heparin-induced thrombocytopenia.

    Evidence FCGR2A transgenic mouse thrombosis models with anti-CD40L and bevacizumab immune complexes, aglycosylated antibody controls

    PMID:18983497 PMID:20585032

    Open questions at the time
    • Relative contribution of platelet serotonin vs. thrombin generation not fully delineated
    • Whether FcγRIIa signaling in thrombosis requires the same ITAM–Syk axis as phagocytosis not proven
  11. 2018 High

    FcγRIIa-expressing platelets were shown to be critical determinants of IgG-dependent anaphylaxis severity in vivo: platelet depletion attenuated anaphylaxis, thrombocythemia exacerbated it, and serotonin released by activated platelets was identified as a key mediator, establishing a platelet–FcγRIIa–serotonin axis in systemic anaphylaxis.

    Evidence Human FCGR2A transgenic mice, platelet depletion/expansion, serotonin blockade, patient cohort correlation

    PMID:29654057

    Open questions at the time
    • Relative importance of platelet vs. myeloid FcγRIIa in human anaphylaxis not resolved
    • Downstream signaling from FcγRIIa to serotonin release machinery not mapped
  12. 2019 High

    Pharmacological profiling with six distinct BTK inhibitors demonstrated that BTK is the critical kinase downstream of FcγRIIa cross-linking for platelet aggregation, secretion, and platelet–neutrophil complex formation, validating BTK as a druggable node in FcγRIIa-driven thromboinflammation.

    Evidence Multiple BTK inhibitors at defined IC50 values, aggregometry, P-selectin FACS, ATP secretion, HIT sera, single-dose pharmacodynamics in volunteers

    PMID:31809536

    Open questions at the time
    • Whether BTK inhibition also blocks FcγRIIa-driven phagocytosis in myeloid cells with equal potency not shown
    • Compensatory kinase pathways in platelet FcγRIIa signaling not explored
  13. 2020 High

    Identification of FcRn as a coreceptor that forms a ternary complex with FcγRIIa and IgG1 immune complexes under acidic endosomal conditions revealed an unanticipated cooperative mechanism by which two Fc receptors jointly amplify innate and adaptive immune responses to IgG ICs.

    Evidence Biochemical ternary complex assays at acidic pH, FcRn knockout/blockade, primary human and mouse cell functional assays, arthritis model

    PMID:32658257

    Open questions at the time
    • Whether FcRn cooperates with FcγRIIa for all IgG subclasses not tested
    • Structural basis of the ternary complex unknown
    • Whether FcRn coreceptor function extends to FcγRIIa-mediated phagocytosis not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of inside-out affinity regulation, the identity of the direct cytoplasmic binding partner of the L-T-L motif that routes Ca²⁺ to phagosomes, whether the FcRn–FcγRIIa coreceptor axis operates across all IgG subclasses and cell types, and how FcγRIIa signaling differentially programs cell-type-specific outcomes (phagocytosis, thrombosis, anaphylaxis, DC maturation).
  • Structural basis of inside-out affinity modulation unknown
  • L-T-L motif binding partner unidentified
  • Cell-type-specific signaling wiring downstream of common ITAM not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 6 R-HSA-109582 Hemostasis 4 R-HSA-5357801 Programmed Cell Death 1
Partners
BTKCD300AFCGRTITGAMKHDRBS1SYKTECTLR9

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 FCGR2A (FcγRIIa/CD32A) encodes an integral membrane glycoprotein with two extracellular Ig-like domains, a single transmembrane domain, and a cytoplasmic domain distinct from FcγRIIb isoforms; expression of the cDNA in transfected cells produces IgG-binding molecules bearing CD32 epitopes, establishing it as a functional IgG receptor. cDNA cloning, sequencing, and transfection expression assays The Journal of experimental medicine High 2529342
1993 The IgG Fc binding site of FcγRII (CD32) maps primarily to the second extracellular domain (D2γ), with epitopes defined by blocking mAbs all residing in D2γ and involving the IgG Fc binding region; domain 1 contributes to overall binding affinity. Chimeric receptor construction, mAb epitope mapping, EA rosette inhibition assays, flow cytometry on transfected cells Journal of immunology High 7679695
1994 FcγRIIa (CD32A) is the sole IgG Fc receptor capable of binding human IgG2; the H131 allotype binds IgG2 with significantly higher affinity than the R131 allotype, and neutrophils homozygous for H/H131 mediate significantly greater phagocytosis of IgG2-opsonized bacteria than R/R131 neutrophils. Immunophenotyping, phagocytosis assays with IgG2-opsonized bacteria in neutrophils from genotyped donors The Journal of infectious diseases High 7930726 7930727
1994 The H131/R131 polymorphism at amino acid 131 of FcγRIIa is determined by a single nucleotide difference (G or A) at base 494 encoding arginine or histidine, which dictates differential affinity for human IgG2. PCR amplification of genomic DNA and Southern analysis with allele-specific oligonucleotide probes Journal of immunological methods High 8046255
1994 FcγRIIa (CD32A) cross-linking on B lymphocytes triggers increases in intracellular Ca2+ ([Ca2+]i), whereas FcγRIIb isoforms do not; FcγRIIa efficiently internalizes IgG aggregates while FcγRIIb1 does not, demonstrating isoform-specific functional differences. Stable transfection of isoforms into mouse IIA1.6 B lymphoma cells, Ca2+ flux measurements, internalization assays, receptor capping assays Journal of immunology High 8283039
1995 Multiple regions of FcγRII contribute to IgG binding: domain 1 contributes to affinity, and two segments of domain 2 (Ser109–Val116 and Ser130–Thr135, including residues Lys113, Pro114, Leu115, Val116, Phe129, and His131) are critical for IgG1 binding; substitution of Asp133 and Pro134 increases binding. Chimeric receptor construction between FcγRII and FcεRIα, site-directed mutagenesis, IgG binding assays, molecular modeling The Journal of biological chemistry High 7673151
1995 FcγRIIa signaling following cross-linking requires activation of Src-family tyrosine kinases and Syk, resulting in tyrosine phosphorylation of Shc and phospholipase Cγ isoforms and a cytosolic Ca2+ transient. Biochemical signaling assays, kinase inhibitor studies, immunoprecipitation Seminars in immunology Medium 7612894
1995 The H131/R131 polymorphism at position 131 of FcγRIIa modulates binding of monoclonal IgG1 antibodies on platelets; the R131 form binds IgG1 mAbs with stronger affinity than H131, and differential platelet activation by mAbs correlates with the allotype-dependent binding affinity. Allotype-specific genotyping, IgG mAb binding assays on platelets from homozygous/heterozygous donors, platelet aggregation measurements Thrombosis and haemostasis Medium 8772237
1996 FcγRIIa (CD32A) cross-linking on dermal microvascular endothelial cells (DMEC) triggers immediate intracellular Ca2+ flux and rapid receptor internalization, demonstrating functional signaling capacity; DMEC express FcγRIIa (not FcγRIIb or FcγRIII) as determined by RT-PCR. Immunohistochemistry, RT-PCR, FACS, intracellular Ca2+ measurement, receptor internalization assay Journal of immunology Medium 8568259
1996 FcγRIIa cross-linking in platelets leads to tyrosine phosphorylation and recruitment of Grb2-binding proteins (38 kDa and 63 kDa) in the particulate fraction; SH3 domains of Grb2 associate with SOS1, SLP-76 (75 kDa), and a 120 kDa protein, linking FcγRIIa to downstream Ras/SOS signaling. GST-Grb2 fusion protein pulldown, immunoprecipitation, SH2/SH3 domain binding assays, phosphoprotein identification by immunoblot Blood Medium 8695800
1996 Mac-1 (CD11b/CD18, αMβ2 integrin) but not p150,95 (CD11c/CD18) associates with FcγRIIA on K562 cells; anti-FcγRII mAbs inhibit Mac-1-mediated cell adhesion but not p150,95-mediated adhesion. Transfection of K562 cells with Mac-1 or p150,95, adhesion inhibition assays with anti-FcγRII mAbs European journal of immunology Medium 8566068
1998 FcγRIIc (CD32) expression on NK cells is determined by an allelic polymorphism in the FcγRIIC gene first extracellular exon that generates either a functional open reading frame or a null allele; donors with the functional allele express CD32 capable of triggering NK-cell cytotoxicity, while null allele donors lack surface CD32 on NK cells. cDNA isolation and sequencing from NK cells, stable transfection, flow cytometry, cytotoxicity assays correlated with allele presence Blood Medium 9516136
1999 FcγRIIa ligation on eosinophils in solution (soluble anti-CD32 mAb or cross-linked IgG) promotes survival by inducing autocrine GM-CSF production, whereas immobilized anti-CD32 mAb or IgG triggers eosinophil apoptosis dependent on β2 integrin engagement. In vitro eosinophil culture with anti-CD32 mAbs in solution vs. immobilized, apoptosis detection (DNA fragmentation, Annexin-V), anti-GM-CSF blocking, anti-CD18 blocking Journal of immunology Medium 10201955
1999 Biochemical characterization established that FcγRIIa binds IgG3 (KD = 0.6 μM) and also IgG4 (KD = 3 μM), extending its known ligand repertoire; both N-linked glycosylation sites on FcγRIIa are occupied. Equilibrium binding analysis of recombinant FcγRIIa with IgG subclasses, electrospray ionization mass spectrometry for glycan characterization, crystallization yielding diffraction-quality crystals at 2.1 Å Immunology letters High 10397151
2000 In resting neutrophils, FcγRIIa (CD32A) is maintained in a low-affinity state for IgG binding; activation with fMLP converts CD32A to a high-affinity state without increasing surface expression, enabling CD32A-dependent immune complex binding and phagocytosis. This affinity modulation was not observed in CHO cells expressing CD32A, indicating a cell-specific mechanism. Use of CD16B-deficient donor neutrophils and anti-CD16 blocking mAbs, fMLP activation, IgG-opsonized erythrocyte rosetting assays, immune complex binding assays Blood High 10648424
2000 CD32 cross-linking in platelets rapidly induces tyrosine phosphorylation and activation of Bruton's tyrosine kinase (Btk) and Tec kinase via a mechanism involving Src family kinases and PI3K through ITAM-mediated recruitment. CD32 cross-linking in human platelets (including XLA patient platelets), immunoprecipitation, phosphopeptide-specific antibodies against Btk regulatory residues, kinase inhibitor studies Blood Medium 10688822
2001 The cytoplasmic tail of FcγRIIa is required for phagolysosome fusion: wild-type FcγRIIa-mediated phagosomes fuse with lysosomes, but a tail-minus FcγRIIa (even when phagocytosis is rescued by complement receptor CR3) fails to support phagolysosome fusion. This function does not require a functional ITAM sequence. Genetic complementation using tail-minus and ITAM-mutant FcγRIIa, fluorescent dextran lysosome labeling, colocalization microscopy, electron microscopy with acid phosphatase detection Blood High 11719384
2001 SAM68 (68 kDa Src-associated protein) is present in human neutrophils, becomes tyrosine-phosphorylated following CD32 ligation, and its association with poly-U RNA decreases upon CD32 stimulation, implicating SAM68 in post-transcriptional regulation downstream of FcγRIIa. Immunoprecipitation, tyrosine phosphorylation assays, poly-U Sepharose pulldown assays after CD32 cross-linking Journal of immunology Medium 11254726
2003 Cross-linking of FcγRII (CD32) with immobilized IgG induces maturation of human monocyte-derived dendritic cells via the NF-κB signaling pathway, accompanied by moderate IL-10 (but not IL-12) secretion and enhanced allogeneic T cell proliferation; this is blocked by anti-CD32 mAb. Cross-linking with immobilized IgG, NF-κB activation assays, cytokine ELISA, allogeneic T cell proliferation assay, anti-CD32 mAb blocking Journal of immunology Medium 12682223
2003 The cytoplasmic L-T-L motif of FcγRIIa controls the spatiotemporal routing of calcium waves to phagosomes: mutation of this motif prevents calcium signal routing to the phagosome and abrogates phagolysosome fusion, despite normal recruitment of lysosome-associated proteins Rab5 and Rab7. High-speed calcium imaging of live cells, mutagenesis of cytoplasmic L-T-L motif, immunofluorescence for Rab5, Rab7, and LAMP-1 Proceedings of the National Academy of Sciences High 12676989
2004 Cross-linking of CD32A in neutrophil plasma membranes causes its recruitment to high-density flotillin-1-positive detergent-resistant membrane (DRM) microdomains prior to tyrosine phosphorylation; Src kinases and Syk are constitutively present in DRMs and tyrosine phosphorylation of CD32A and Syk is inhibited by the Src kinase inhibitor PP2 and by methyl-β-cyclodextrin. Purified neutrophil plasma membranes, DRM fractionation, immunoblotting, Src kinase inhibitor PP2, methyl-β-cyclodextrin cholesterol depletion The Biochemical journal Medium 15130090
2005 DNA-containing immune complexes from lupus serum activate plasmacytoid DCs via cooperative interaction between FcγRIIa (CD32) and TLR9: CD32 internalizes SLE immune complexes into a subcellular compartment co-containing TLR9, and only CD32+ PDCs (not CD32- PDCs) respond to SLE-ICs, defining a pathway where CD32 delivers immune complexes to lysosomal TLR9. Colocalization microscopy, sorting of CD32+ vs CD32- PDCs, cytokine/chemokine production assays, blocking with anti-CD32 The Journal of clinical investigation High 15668740
2006 FcγRIIA (CD32) mediates enhanced dengue virus immune complex infectivity more effectively than FcγRIA; abrogation of FcγRIIA ITAM signaling by tyrosine-to-phenylalanine mutagenesis impairs phagocytosis equally but does not impair dengue virus immune complex infectivity, revealing a signaling-independent mechanism of viral internalization via FcγRIIA. Site-directed mutagenesis of ITAM tyrosines, transfection into COS-7 cells, dengue virus replication assays (plaque assay and flow cytometry) Journal of virology High 17005690
2007 Antiendothelial cell antibodies (AECAs) bound to endothelial cells enhance PMN adhesion through FcγRIIa in an E-selectin-, CXCR1/2-, and β2-integrin-dependent mechanism requiring cooperation between FcγRIIa and CXCR1/2; this mechanism is distinct from immune complex-mediated FcγRIIIb-dependent PMN adhesion. Adenoviral transduction of endothelial cells, neutralizing antibodies to E-selectin/CXCR1/2/β2-integrins, anti-FcγRIIa blocking, pertussis toxin inhibition, AECA IgG from SLE patients Blood High 17244681
2007 CD300a (IRp60), an ITIM-containing inhibitory receptor, colligates with FcγRIIa (CD32A) on neutrophils to inhibit CD32A-mediated signaling but not TLR4-mediated ROS production, demonstrating selective inhibitory control of FcγRIIa-dependent responses. Co-ligation experiments with anti-CD300a and anti-CD32A in neutrophils, ROS production assays, signaling inhibition assays Molecular immunology Medium 17588661
2008 Bevacizumab immune complexes (with VEGF) activate platelets via FcγRIIa and cause thrombosis in FcγRIIa transgenic mice; VEGF's heparin-binding domain is required, and heparin promotes Bev IC deposition on platelets in a mechanism resembling heparin-induced thrombocytopenia. In vitro platelet activation assays, FcγRIIa transgenic mice thrombosis model, aglycosylated antibody controls, heparin-binding domain analysis Journal of thrombosis and haemostasis High 18983497
2008 IVIg and CMVIg induce CD32-dependent platelet aggregation in vitro; the aggregation is completely abrogated by an anti-CD32 blocking antibody (AT10), demonstrating that activating Fc domains in immunoglobulin preparations directly engage platelet FcγRIIa to trigger aggregation. In vitro aggregometry with platelet concentrates, anti-CD32 mAb (AT10) blocking, CD62P expression by FACS, sCD40L ELISA The British journal of dermatology Medium 18565176
2009 FcγRIIa (CD32A) association with lipid raft microdomains regulates its IgG binding activity: cholesterol depletion or sequestration inhibits CD32A-mediated IgG binding; CD32A mutants with reduced lipid raft association (A224S and C241A) show decreased IgG binding; GPI-anchored (constitutively raft-associated) CD32A displays increased IgG binding capacity. Cholesterol depletion/sequestration, site-directed mutagenesis of CD32A (A224S, C241A), GPI-anchored CD32A construct, IgG binding assays Journal of immunology High 19494328
2009 The R allele of CD32A has significantly lower binding affinity not only to IgG2 but also to IgG1 and IgG3 compared with the H allele; CD32A(H)-Ig outcompetes CD32A(R)-Ig for immune complex binding, whereas CD32A(R)-Ig cannot cross-block CD32A(H) binding, as shown by 2D affinity measurements. Ig fusion proteins of CD32A alleles, competition binding assays, 2D affinity measurements, cell surface CD32A blocking studies Journal of immunology High 20007585
2010 Anti-CD40L immune complex-induced thrombosis is FcγRIIa-dependent: anti-CD40L ICs cause shock, thrombocytopenia, and pulmonary thrombi in FCGR2A transgenic mice but not wild-type mice; aglycosylated antibody (which cannot bind FcγRIIa) fails to cause these effects. FCGR2A transgenic mouse model, i.v. injection of preformed ICs, aglycosylated antibody control, thrombin inhibitor pretreatment, histopathology of pulmonary thrombi Journal of immunology High 20585032
2011 CRP-derived peptide 201–206 inhibits neutrophil adhesion to endothelial cells and platelet-mediated neutrophil capture via CD32 (FcγRII); anti-CD32 but not anti-CD16 or anti-CD64 mAb blocks these inhibitory actions; specific residues Lys201, Gln203, and Trp205 are required for peptide-CD32 interaction. Anti-CD32/CD16/CD64 mAb blocking of peptide effects, alanine-substitution peptide analogues, neutrophil adhesion under shear flow, platelet P-selectin assays Journal of leukocyte biology Medium 21934067
2017 CRP binds surface CD32 (FcγRII) on myeloma cells and activates a p38 MAPK–Twist signaling pathway that enhances secretion of osteolytic cytokines and promotes osteoclastogenesis and bone destruction in vivo. CRP-CD32 binding assays, p38 MAPK activation and Twist pathway analysis, in vivo human bone graft/myeloma xenograft model, cytokine secretion assays Science signaling Medium 29233917
2018 FcγRIIA/CD32A-expressing platelets are directly activated by IgG immune complexes in vivo and are critical determinants of IgG-dependent anaphylaxis severity: platelet depletion attenuates anaphylaxis, thrombocythemia worsens it, and serotonin released by activated platelets contributes to severity. FcγRIIA-expressing platelets are sufficient to restore anaphylaxis susceptibility in resistant mice. Human FcγRIIA-expressing mouse models, platelet depletion, thrombocythemia induction, platelet activation by IgG ICs in vivo, serotonin blockade, patient cohort correlation Science immunology High 29654057
2019 BTK is a key downstream mediator of FcγRIIA (CD32a)-induced platelet activation; BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, evobrutinib, fenebrutinib) potently block FcγRIIA cross-linking-induced platelet aggregation, secretion, P-selectin expression, and platelet-neutrophil complex formation at clinically relevant concentrations. FcγRIIA cross-linking in human blood, aggregometry with BTK inhibitors at defined IC50 values, P-selectin FACS, ATP secretion assays, HIT patient sera stimulation, single oral dose pharmacodynamics in volunteers Blood advances High 31809536
2020 FcRn acts as a coreceptor for CD32a (FcγRIIa): CD32aH (H131 variant) more avidly binds human IgG1 immune complexes than CD32aR and forms a ternary complex with FcRn under acidic conditions; both CD32a variants require FcRn to induce innate and adaptive immune responses to IgG1 ICs, with responses augmented for CD32aH. FcRn blockade reduced inflammation in an arthritis model without lowering circulating autoantibody levels. Binding assays (CD32aH vs CD32aR with IgG1 IC), ternary complex formation assays under acidic pH, primary human and mouse cell functional assays, FcRn knockout/blockade, rheumatoid arthritis model The Journal of experimental medicine High 32658257
2020 SRF231, a human IgG4 anti-CD47 antibody, exerts antitumor activity via dual engagement of macrophage-derived CD32a: its Fc domain engages CD32a to drive FcγR-mediated phagocytosis of cancer cells and acts as a scaffold to drive CD47-mediated death signaling into tumor cells; both mechanisms are CD32a-dependent. In vitro macrophage:tumor cell co-culture, FcγR blocking, macrophage depletion, xenograft mouse models, cytokine analysis Journal for immunotherapy of cancer Medium 32345627

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. The Journal of clinical investigation 666 15668740
2007 FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 383 17704420
1989 Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes. The Journal of experimental medicine 308 2529342
2011 Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nature genetics 280 22081228
2017 CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses. Nature 193 28297712
1995 Skewed distribution of IgG Fc receptor IIa (CD32) polymorphism is associated with renal disease in systemic lupus erythematosus patients. Arthritis and rheumatism 171 8849356
1994 Fc gamma receptor IIa (CD32) polymorphism in fulminant meningococcal septic shock in children. The Journal of infectious diseases 157 7930726
1994 Fc gamma receptor IIa (CD32) heterogeneity in patients with recurrent bacterial respiratory tract infections. The Journal of infectious diseases 145 7930727
2010 Anti-CD40L immune complexes potently activate platelets in vitro and cause thrombosis in FCGR2A transgenic mice. Journal of immunology (Baltimore, Md. : 1950) 139 20585032
2008 Bevacizumab immune complexes activate platelets and induce thrombosis in FCGR2A transgenic mice. Journal of thrombosis and haemostasis : JTH 134 18983497
2009 Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B. Human mutation 131 19309690
1994 Ethnic variation in frequency of an allelic polymorphism of human Fc gamma RIIA determined with allele specific oligonucleotide probes. Journal of immunological methods 126 8046255
2019 The Human FcγRII (CD32) Family of Leukocyte FcR in Health and Disease. Frontiers in immunology 117 30941127
2007 Monoclonal antibodies capable of discriminating the human inhibitory Fcgamma-receptor IIB (CD32B) from the activating Fcgamma-receptor IIA (CD32A): biochemical, biological and functional characterization. Immunology 115 17386079
1994 Functional analysis of human Fc gamma RII (CD32) isoforms expressed in B lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 113 8283039
2006 Differential enhancement of dengue virus immune complex infectivity mediated by signaling-competent and signaling-incompetent human Fcgamma RIA (CD64) or FcgammaRIIA (CD32). Journal of virology 103 17005690
1998 Expression of functional CD32 molecules on human NK cells is determined by an allelic polymorphism of the FcgammaRIIC gene. Blood 97 9516136
2017 Association of Polymorphisms in FCGR2A and FCGR3A With Degree of Trastuzumab Benefit in the Adjuvant Treatment of ERBB2/HER2-Positive Breast Cancer: Analysis of the NSABP B-31 Trial. JAMA oncology 91 27812689
2018 CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells. Science translational medicine 88 29669853
2006 FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 88 16682723
2000 Rapid tyrosine phosphorylation and activation of Bruton's tyrosine/Tec kinases in platelets induced by collagen binding or CD32 cross-linking. Blood 82 10688822
1995 Function of human Fc gamma RIIA and Fc gamma RIIIB. Seminars in immunology 77 7612894
2003 Association of Fcgamma receptor IIa (CD32) polymorphism with severe malaria in West Africa. The American journal of tropical medicine and hygiene 74 14740869
2018 Platelets expressing IgG receptor FcγRIIA/CD32A determine the severity of experimental anaphylaxis. Science immunology 65 29654057
2007 The CD300a (IRp60) inhibitory receptor is rapidly up-regulated on human neutrophils in response to inflammatory stimuli and modulates CD32a (FcgammaRIIa) mediated signaling. Molecular immunology 65 17588661
2001 Fcgamma receptor IIa (CD32) polymorphism is associated with protection of infants against high-density Plasmodium falciparum infection. VII. Asembo Bay Cohort Project. The Journal of infectious diseases 64 11398118
2018 CD32 expression is associated to T-cell activation and is not a marker of the HIV-1 reservoir. Nature communications 60 30013105
1993 Mapping epitopes of human Fc gamma RII (CDw32) with monoclonal antibodies and recombinant receptors. Journal of immunology (Baltimore, Md. : 1950) 60 7679695
2004 FCGR3A and FCGR2A polymorphisms may not correlate with response to alemtuzumab in chronic lymphocytic leukemia. Blood 59 15217834
1995 Multiple regions of human Fc gamma RII (CD32) contribute to the binding of IgG. The Journal of biological chemistry 56 7673151
1996 Dermal microvascular endothelial cells express CD32 receptors in vivo and in vitro. Journal of immunology (Baltimore, Md. : 1950) 53 8568259
2000 Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function. Blood 52 10648424
1990 Different isoforms of human FcRII distinguished by CDw32 antibodies. Journal of immunology (Baltimore, Md. : 1950) 49 2138195
2019 Oral Bruton tyrosine kinase inhibitors block activation of the platelet Fc receptor CD32a (FcγRIIA): a new option in HIT? Blood advances 48 31809536
2016 Neuroblastoma patients with high-affinity FCGR2A, -3A and stimulatory KIR 2DS2 treated by long-term infusion of anti-GD2 antibody ch14.18/CHO show higher ADCC levels and improved event-free survival. Oncoimmunology 48 27999754
2020 The Fully human anti-CD47 antibody SRF231 exerts dual-mechanism antitumor activity via engagement of the activating receptor CD32a. Journal for immunotherapy of cancer 47 32345627
2003 Cross-linking of CD32 induces maturation of human monocyte-derived dendritic cells via NF-kappa B signaling pathway. Journal of immunology (Baltimore, Md. : 1950) 47 12682223
1997 Fc gamma RIIa polymorphism in systemic lupus erythematosus. Annals of the rheumatic diseases 47 9496155
2012 Clinical outcome of patients with follicular lymphoma receiving chemoimmunotherapy in the PRIMA study is not affected by FCGR3A and FCGR2A polymorphisms. Blood 46 22885164
2006 Association of FCGR2A and FCGR2A-FCGR3A haplotypes with susceptibility to giant cell arteritis. Arthritis research & therapy 46 16846526
2018 The role of CD32 during HIV-1 infection. Nature 44 30232425
1996 Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking. Blood 44 8695800
2009 Association of FcgammaRIIa (CD32a) with lipid rafts regulates ligand binding activity. Journal of immunology (Baltimore, Md. : 1950) 43 19494328
1999 Ligation of Fc gamma RII (CD32) pivotally regulates survival of human eosinophils. Journal of immunology (Baltimore, Md. : 1950) 43 10201955
2022 Pentraxin 3 regulated by miR-224-5p modulates macrophage reprogramming and exacerbates osteoarthritis associated synovitis by targeting CD32. Cell death & disease 42 35739102
2014 FcγRIII (CD16)-mediated ADCC by NK cells is regulated by monocytes and FcγRII (CD32). European journal of immunology 42 25100508
1993 Tissue distribution of human IgG Fc receptors CD16, CD32 and CD64: an immunohistochemical study. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 42 8323742
2020 FcRn is a CD32a coreceptor that determines susceptibility to IgG immune complex-driven autoimmunity. The Journal of experimental medicine 40 32658257
2007 Antiendothelial cell antibodies mediate enhanced leukocyte adhesion to cytokine-activated endothelial cells through a novel mechanism requiring cooperation between Fc{gamma}RIIa and CXCR1/2. Blood 40 17244681
1995 Role of Fc gamma RIIA gene polymorphism in human platelet activation by monoclonal antibodies. Thrombosis and haemostasis 40 8772237
2009 Dynamics of the interaction of human IgG subtype immune complexes with cells expressing R and H allelic forms of a low-affinity Fc gamma receptor CD32A. Journal of immunology (Baltimore, Md. : 1950) 39 20007585
1989 Human basophils selectively express the Fc gamma RII (CDw32) subtype of IgG receptor. The Journal of allergy and clinical immunology 38 2532230
2018 CD32-Expressing CD4 T Cells Are Phenotypically Diverse and Can Contain Proviral HIV DNA. Frontiers in immunology 36 29780387
2020 CD32+CD4+ T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency. Cell reports 35 32075737
2015 Variation at FCGR2A and functionally related genes is associated with the response to anti-TNF therapy in rheumatoid arthritis. PloS one 35 25848939
2019 In vitro elimination of epidermal growth factor receptor-overexpressing cancer cells by CD32A-chimeric receptor T cells in combination with cetuximab or panitumumab. International journal of cancer 34 31479522
2003 Signal sequence within Fc gamma RIIA controls calcium wave propagation patterns: apparent role in phagolysosome fusion. Proceedings of the National Academy of Sciences of the United States of America 34 12676989
1993 Expression of the Fc receptor for IgG (Fc gamma RII/CDw32) by human circulating T and B lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 34 8496609
2014 A genetic variant rs1801274 in FCGR2A as a potential risk marker for Kawasaki disease: a case-control study and meta-analysis. PloS one 33 25093412
2007 Study of common functional genetic polymorphisms of FCGR2A, 3A and 3B genes and the risk for cryptococcosis in HIV-uninfected patients. Medical mycology 33 17710620
2017 C-reactive protein promotes bone destruction in human myeloma through the CD32-p38 MAPK-Twist axis. Science signaling 31 29233917
2019 FCGR3A and FCGR2A Genotypes Differentially Impact Allograft Rejection and Patients' Survival After Lung Transplant. Frontiers in immunology 30 31249568
2017 IL-3 up-regulates and activates human eosinophil CD32 and αMβ2 integrin causing degranulation. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 30 28000949
1999 Biochemical analysis and crystallisation of Fc gamma RIIa, the low affinity receptor for IgG. Immunology letters 30 10397151
2017 Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease. PloS one 29 28886140
2016 Associations between PTPRC rs10919563 A/G and FCGR2A R131H polymorphisms and responsiveness to TNF blockers in rheumatoid arthritis: a meta-analysis. Rheumatology international 28 27074847
2009 FcgammaRIIa (CD32) polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan. Malaria journal 28 19284648
2004 Recruitment of the cross-linked opsonic receptor CD32A (FcgammaRIIA) to high-density detergent-resistant membrane domains in human neutrophils. The Biochemical journal 28 15130090
1998 A regulatory role for Fcgamma receptors CD16 and CD32 in the development of murine B cells. Blood 28 9763567
2012 FCGR2A/CD32A and FCGR3A/CD16A variants and EULAR response to tumor necrosis factor-α blockers in psoriatic arthritis: a longitudinal study with 6 months of followup. The Journal of rheumatology 27 22467926
2006 Anti-OxLDL IgG blocks OxLDL interaction with CD36, but promotes FcgammaR, CD32A-dependent inflammatory cell adhesion. Immunology letters 27 17081622
1996 The beta 2 integrin Mac-1 but not p150,95 associates with Fc gamma RIIA. European journal of immunology 27 8566068
2020 Human Liver Macrophage Subsets Defined by CD32. Frontiers in immunology 26 33101269
2016 Fc Gamma Receptor IIA (CD32A) R131 Polymorphism as a Marker of Genetic Susceptibility to Sepsis. Inflammation 26 26490967
2010 Analysis of MIF, FCGR2A and FCGR3A gene polymorphisms with susceptibility to pulmonary tuberculosis in Moroccan population. Journal of genetics and genomics = Yi chuan xue bao 26 20439102
2009 FCGR2B gene polymorphism rather than FCGR2A, FCGR3A and FCGR3B is associated with anti-GBM disease in Chinese. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 26 19640933
2001 Levels of expression of Fcgamma receptor IIA (CD32) are decreased on peripheral blood monocytes in patients with severe atherosclerosis. Atherosclerosis 26 11223444
1997 Fc gammaRII (CD32) is linked to apoptotic pathways in murine granulocyte precursors and mature eosinophils. Blood 26 9242561
2007 Interethnic differences in carriage of haemoglobin AS and Fcgamma receptor IIa (CD32) genotypes in children living in eastern Sudan. Acta tropica 25 18022136
2001 The cytoplasmic domain of FcgammaRIIA (CD32) participates in phagolysosome formation. Blood 25 11719384
1999 Monoclonal Lym-1 antibody-dependent cytolysis by neutrophils exposed to granulocyte-macrophage colony-stimulating factor: intervention of FcgammaRII (CD32), CD11b-CD18 integrins, and CD66b glycoproteins. Blood 25 10233903
2006 Neutrophil responsiveness to IgG, as determined by fixed ratios of mRNA levels for activating and inhibitory FcgammaRII (CD32), is stable over time and unaffected by cytokines. Blood 24 16551965
2004 Fc gamma RIIa polymorphism: a susceptibility factor for immune complex-mediated lupus nephritis in Brazilian patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 24 15004265
2011 C-reactive protein-derived peptide 201-206 inhibits neutrophil adhesion to endothelial cells and platelets through CD32. Journal of leukocyte biology 23 21934067
1994 CD31 (PECAM-1), CDw32 (Fc gamma RII), and anti-HLA class I monoclonal antibodies recognize phosphotyrosine-containing proteins on the surface of human neutrophils. Journal of immunology (Baltimore, Md. : 1950) 23 7515918
2016 Association of FCGR2A rs1801274 polymorphism with susceptibility to autoimmune diseases: A meta-analysis. Oncotarget 22 27270653
2008 Intravenous immunoglobulins induce CD32-mediated platelet aggregation in vitro. The British journal of dermatology 22 18565176
1995 Granulocyte colony-stimulating factor (G-CSF) administration increases PMN CD32 (FcRII) expression and FcR-related functions. Haematologica 22 7543071
2015 FCGR2A, FCGR3A, FCGR3B polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis. Clinical and experimental rheumatology 21 26314337
2011 E-selectin rs5361 and FCGR2A rs1801274 variants were associated with increased risk of gastric cancer in a Chinese population. Molecular carcinogenesis 21 21780194
2023 Modeling of clinical phenotypes in systemic lupus erythematosus based on the platelet transcriptome and FCGR2a genotype. Journal of translational medicine 20 37029410
2019 CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype. Mucosal immunology 20 31239514
2019 Association of TNF-α rs1800629, CASP3 rs72689236 and FCGR2A rs1801274 Polymorphisms with Susceptibility to Kawasaki Disease: A Comprehensive Meta-Analysis. Fetal and pediatric pathology 20 31884867
2011 Polymorphisms of CD16A and CD32 Fcγ receptors and circulating immune complexes in Ménière's disease: a case-control study. BMC medical genetics 20 21208440
2009 Age related variation in expression of CD21 and CD32 on bovine lymphocytes: a cross-sectional study. Veterinary immunology and immunopathology 20 19243842
2022 The FCGR2A rs1801274 polymorphism was associated with the risk of death among COVID-19 patients. Clinical immunology (Orlando, Fla.) 19 35149195
2012 ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer who were treated with first-line taxane plus trastuzumab chemotherapy. Oncology 19 22906996
2015 FCGR2A Promoter Methylation and Risks for Intravenous Immunoglobulin Treatment Responses in Kawasaki Disease. Mediators of inflammation 18 26089602
2001 Evidence for a role for SAM68 in the responses of human neutrophils to ligation of CD32 and to monosodium urate crystals. Journal of immunology (Baltimore, Md. : 1950) 18 11254726
2004 The role of beta-catenin, TGF beta 3, NGF2, FGF2, IGFR2, and BMP4 in the pathogenesis of mesenteric sclerosis and angiopathy in midgut carcinoids. Human pathology 17 15188132