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Gene Review

FCGR2A  -  Fc fragment of IgG, low affinity IIa,...

Homo sapiens

Synonyms: CD32, CD32A, CDw32, FCG2, FCGR2, ...
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Disease relevance of FCGR2A


High impact information on FCGR2A

  • Human resting B lymphocytes entered a state of sustained proliferation when incubated with both the mouse fibroblastic Ltk- cell line that had been transfected with the human Fc receptor (Fc gamma RII/CDw32) and monoclonal antibodies to CD40 [5].
  • A murine macrophage cell line, but not a fibroblast cell line, that was transfected with human Fc gamma RIIA mediated phagocytosis and an intracellular Ca2+ concentration ([Ca2+]i) flux upon cross-linking of human Fc gamma RIIA [6].
  • However, only wild-type transfectants phagocytosed labeled erythrocytes and fluxed [Ca2+]i. Thus, the cytoplasmic domain of human Fc gamma RIIA contains distinct functional regions [6].
  • We show here that, when coaggregated to these receptors, Fc gamma RIIB inhibit Fc epsilon RI-, Fc gamma RIIA-, and TCR-dependent cell activation [7].
  • We conclude that CD32 is an antigen uptake receptor on pDCs and that antigen presentation by pDCs is of particular relevance when circulating antibodies are present [8].

Chemical compound and disease context of FCGR2A


Biological context of FCGR2A


Anatomical context of FCGR2A

  • FCGR2A was highly expressed in adipocytes in both depots and this was verified by immunohistochemistry [11].
  • In this study, we analyzed the role of Fc gamma RIIa in binding of stable hIgG-subclass dimers, and in induction of T cell mitogenesis using chimeric anti-CD3 mAb [12].
  • The Fc gamma R-negative B-cell line IIA1.6 was transfected with wild-type or mutant human Fc gamma RIIa and IIb molecules [4].
  • Human basophils selectively express the Fc gamma RII (CDw32) subtype of IgG receptor [13].
  • This work reveals a new role for CRP in modulating the immune system by inhibiting DC differentiation, maturation and functions mainly through FcgammaRIIa/CD32 [14].

Associations of FCGR2A with chemical compounds


Physical interactions of FCGR2A

  • We observed that binding of the Fab parts of 3G8 mAb to two Fc gamma RIIIb molecules and binding of the Fc part to one Fc gamma RIIa molecule is required, because a bispecific antibody, 2B1, in which only one 3G8 Fab is present, did not induce neutrophil activation [19].
  • The cross-linking of Fc gamma RIIa by complexed IgG triggers activation of protein tyrosine kinase and internalization of immune complexes [20].

Enzymatic interactions of FCGR2A


Regulatory relationships of FCGR2A

  • Here we report that Fc gamma RIIa clustering induces SHP-1 phosphatase activity in THP-1 cells [16].
  • Fc gamma RIIa is expressed on natural IFN-alpha-producing cells (plasmacytoid dendritic cells) and is required for the IFN-alpha production induced by apoptotic cells combined with lupus IgG [22].
  • Molecular characterization of FcgammaRIIc isoforms expressed by the CD32+ donors revealed that the majority of donors expressed the FcgammaRIIc1 isoform [23].
  • T cell-independent differentiation of sIgD+ and sIgD- B cells could be achieved by simultaneous crosslinking of sIgs and CD40 in the presence of a mouse Ltk- cell line stably expressing human CDw32/Fc gamma RII (CDw32 L cells) [24].
  • Mechanistic studies into the IgE class switch process demonstrated that IL-4/anti-CD40-induced IgE germline gene transcription and B-cell proliferation were not affected by CD32 ligation [25].

Other interactions of FCGR2A


Analytical, diagnostic and therapeutic context of FCGR2A


  1. FCGR3A and FCGR2A polymorphisms may not correlate with response to alemtuzumab in chronic lymphocytic leukemia. Lin, T.S., Flinn, I.W., Modali, R., Lehman, T.A., Webb, J., Waymer, S., Moran, M.E., Lucas, M.S., Farag, S.S., Byrd, J.C. Blood (2005) [Pubmed]
  2. FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor. Cheung, N.K., Sowers, R., Vickers, A.J., Cheung, I.Y., Kushner, B.H., Gorlick, R. J. Clin. Oncol. (2006) [Pubmed]
  3. Association of FCGR2A and FCGR2A-FCGR3A haplotypes with susceptibility to giant cell arteritis. Morgan, A.W., Robinson, J.I., Barrett, J.H., Martin, J., Walker, A., Babbage, S.J., Ollier, W.E., Gonzalez-Gay, M.A., Isaacs, J.D. Arthritis Res. Ther. (2006) [Pubmed]
  4. Identification of signaling motifs within human Fc gamma RIIa and Fc gamma RIIb isoforms. Van den Herik-Oudijk, I.E., Capel, P.J., van der Bruggen, T., Van de Winkel, J.G. Blood (1995) [Pubmed]
  5. Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Banchereau, J., de Paoli, P., Vallé, A., Garcia, E., Rousset, F. Science (1991) [Pubmed]
  6. Regulation of phagocytosis and [Ca2+]i flux by distinct regions of an Fc receptor. Odin, J.A., Edberg, J.C., Painter, C.J., Kimberly, R.P., Unkeless, J.C. Science (1991) [Pubmed]
  7. The same tyrosine-based inhibition motif, in the intracytoplasmic domain of Fc gamma RIIB, regulates negatively BCR-, TCR-, and FcR-dependent cell activation. Daëron, M., Latour, S., Malbec, O., Espinosa, E., Pina, P., Pasmans, S., Fridman, W.H. Immunity (1995) [Pubmed]
  8. Plasmacytoid dendritic cells of melanoma patients present exogenous proteins to CD4+ T cells after Fc gamma RII-mediated uptake. Benitez-Ribas, D., Adema, G.J., Winkels, G., Klasen, I.S., Punt, C.J., Figdor, C.G., de Vries, I.J. J. Exp. Med. (2006) [Pubmed]
  9. Biochemical analysis and crystallisation of Fc gamma RIIa, the low affinity receptor for IgG. Powell, M.S., Barton, P.A., Emmanouilidis, D., Wines, B.D., Neumann, G.M., Peitersz, G.A., Maxwell, K.F., Garrett, T.P., Hogarth, P.M. Immunol. Lett. (1999) [Pubmed]
  10. Fc gamma RIIA H/R 131 polymorphism, subclass-specific IgG anti-heparin/platelet factor 4 antibodies and clinical course in patients with heparin-induced thrombocytopenia and thrombosis. Arepally, G., McKenzie, S.E., Jiang, X.M., Poncz, M., Cines, D.B. Blood (1997) [Pubmed]
  11. Plasma cells and Fc receptors in human adipose tissue--lipogenic and anti-inflammatory effects of immunoglobulins on adipocytes. Palming, J., Gabrielsson, B.G., Jennische, E., Smith, U., Carlsson, B., Carlsson, L.M., Lönn, M. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  12. On the interaction of IgG subclasses with the low affinity Fc gamma RIIa (CD32) on human monocytes, neutrophils, and platelets. Analysis of a functional polymorphism to human IgG2. Parren, P.W., Warmerdam, P.A., Boeije, L.C., Arts, J., Westerdaal, N.A., Vlug, A., Capel, P.J., Aarden, L.A., van de Winkel, J.G. J. Clin. Invest. (1992) [Pubmed]
  13. Human basophils selectively express the Fc gamma RII (CDw32) subtype of IgG receptor. Anselmino, L.M., Perussia, B., Thomas, L.L. J. Allergy Clin. Immunol. (1989) [Pubmed]
  14. C-reactive protein impairs human CD14(+) monocyte-derived dendritic cell differentiation, maturation and function. Zhang, R., Becnel, L., Li, M., Chen, C., Yao, Q. Eur. J. Immunol. (2006) [Pubmed]
  15. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. Weng, W.K., Levy, R. J. Clin. Oncol. (2003) [Pubmed]
  16. The protein-tyrosine phosphatase SHP-1 associates with the phosphorylated immunoreceptor tyrosine-based activation motif of Fc gamma RIIa to modulate signaling events in myeloid cells. Ganesan, L.P., Fang, H., Marsh, C.B., Tridandapani, S. J. Biol. Chem. (2003) [Pubmed]
  17. High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. Nomura, S., Tandon, N.N., Nakamura, T., Cone, J., Fukuhara, S., Kambayashi, J. Atherosclerosis (2001) [Pubmed]
  18. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Kim, D.H., Jung, H.D., Kim, J.G., Lee, J.J., Yang, D.H., Park, Y.H., Do, Y.R., Shin, H.J., Kim, M.K., Hyun, M.S., Sohn, S.K. Blood (2006) [Pubmed]
  19. The anti-Fc gamma RIII mAb 3G8 induces neutrophil activation via a cooperative actin of Fc gamma RIIIb and Fc gamma RIIa. Vossebeld, P.J., Homburg, C.H., Roos, D., Verhoeven, A.J. Int. J. Biochem. Cell Biol. (1997) [Pubmed]
  20. Expression of low-affinity Fc gamma receptor by a human metastatic melanoma line. Cassard, L., Dragon-Durey, M.A., Ralli, A., Tartour, E., Salamero, J., Fridman, W.H., Sautès-Fridman, C. Immunol. Lett. (2000) [Pubmed]
  21. Clustering of the platelet Fc gamma receptor induces noncovalent association with the tyrosine kinase p72syk. Chacko, G.W., Duchemin, A.M., Coggeshall, K.M., Osborne, J.M., Brandt, J.T., Anderson, C.L. J. Biol. Chem. (1994) [Pubmed]
  22. Fc gamma RIIa is expressed on natural IFN-alpha-producing cells (plasmacytoid dendritic cells) and is required for the IFN-alpha production induced by apoptotic cells combined with lupus IgG. Båve, U., Magnusson, M., Eloranta, M.L., Perers, A., Alm, G.V., Rönnblom, L. J. Immunol. (2003) [Pubmed]
  23. Allelic polymorphisms in the FcgammaRIIC gene can influence its function on normal human natural killer cells. Ernst, L.K., Metes, D., Herberman, R.B., Morel, P.A. J. Mol. Med. (2002) [Pubmed]
  24. Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A. Defrance, T., Vanbervliet, B., Brière, F., Durand, I., Rousset, F., Banchereau, J. J. Exp. Med. (1992) [Pubmed]
  25. Inhibition of immunoglobulin E synthesis through Fc gammaRII (CD32) by a mechanism independent of B-cell receptor co-cross-linking. Horejs-Hoeck, J., Hren, A., Mudde, G.C., Woisetschläger, M. Immunology (2005) [Pubmed]
  26. Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility. Kyogoku, C., Dijstelbloem, H.M., Tsuchiya, N., Hatta, Y., Kato, H., Yamaguchi, A., Fukazawa, T., Jansen, M.D., Hashimoto, H., van de Winkel, J.G., Kallenberg, C.G., Tokunaga, K. Arthritis Rheum. (2002) [Pubmed]
  27. Activation of three classes of nonreceptor tyrosine kinases following Fc gamma receptor crosslinking in human monocytes. Pan, X.Q., Darby, C., Indik, Z.K., Schreiber, A.D. Clin. Immunol. (1999) [Pubmed]
  28. Function of human Fc gamma RIIA and Fc gamma RIIIB. Unkeless, J.C., Shen, Z., Lin, C.W., DeBeus, E. Semin. Immunol. (1995) [Pubmed]
  29. Saliva: a convenient source of DNA for analysis of bi-allelic polymorphisms of Fc gamma receptor IIA (CD32) and Fc gamma receptor IIIB (CD16). van Schie, R.C., Wilson, M.E. J. Immunol. Methods (1997) [Pubmed]
  30. An Fc gamma RIII (CD16)-specific autoantibody from a patient with progressive systemic sclerosis. Szegedi, A., Boros, P., Chen, J., Kaffina, M., Bona, C., Unkeless, J.C. Immunol. Lett. (1993) [Pubmed]
  31. Skewed distribution of IgG Fc receptor IIa (CD32) polymorphism is associated with renal disease in systemic lupus erythematosus patients. Duits, A.J., Bootsma, H., Derksen, R.H., Spronk, P.E., Kater, L., Kallenberg, C.G., Capel, P.J., Westerdaal, N.A., Spierenburg, G.T., Gmelig-Meyling, F.H. Arthritis Rheum. (1995) [Pubmed]
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