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Gene Review

FCGR2B  -  Fc fragment of IgG, low affinity IIb,...

Homo sapiens

Synonyms: CD32, CD32B, CDw32, FCG2, FCGR2, ...
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Disease relevance of FCGR2B


High impact information on FCGR2B

  • Mast cells and basophils co-express Fc gamma RIIb, a low affinity receptor containing an immunoreceptor tyrosine-based inhibitory motif and whose co-aggregation with Fc epsilon RI can block Fc epsilon RI-mediated reactivity [5].
  • Neutrophils carry Fc receptor II (FcRII; CDw32) and FcRIII (CD16) which both bind IgG-containing immune complexes, leading to phagocytosis of the complex and activation of the neutrophil [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].
  • The same tyrosine-based inhibitory motif (ITIM), which is highly conserved in murine and human Fc gamma RIIB and that was previously shown to inhibit BCR-dependent B cell activation, was required to regulate TCR- and FcR-dependent cell activation [7].
  • The same tyrosine-based inhibition motif, in the intracytoplasmic domain of Fc gamma RIIB, regulates negatively BCR-, TCR-, and FcR-dependent cell activation [7].

Chemical compound and disease context of FCGR2B

  • The biotinylated peptides R(255)-P(271) and T(256)-P(271) complexed by avidin exhibited functional activity; they induced Fc gamma RIIb-mediated inhibition of the BCR-triggered Ca(2+) response of human Burkitt lymphoma cells, and inflammatory cytokine production (TNF-alpha and IL-6) by the human monocyte cell line MonoMac [8].
  • K1m also expresses Fc receptors for immunoglobulin G (IgG) (CD64, CD32, and CD16) and can be shown to phagocytose polystyrene latex beads, as well as neuroblastoma cells in the presence of tumour-specific monoclonal antibody (mAb) [9].
  • The functions were the following: respiratory burst; secretion of glutamate, interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha); toxicity of culture supernatants towards SH-SY5Y human neuroblastoma cells; and expression of the inflammatory surface markers HLA-DR and Fcgamma RII (CDw32) [10].

Biological context of FCGR2B


Anatomical context of FCGR2B

  • In this study, we examined the impact of FCGR2B c.695T>C on the functional properties of FcgammaRIIB by expressing each allele product in a human B cell line ST486 lacking endogenous FcgammaRIIB [15].
  • Three different classes of Fc receptors for IgG (Fc gamma R) are currently distinguished in humans, of which polymorphonuclear phagocytes (PMN) normally express both low-affinity receptor classes--Fc gamma RII (CD32) and Fc gamma RIII (CD16) [16].
  • Dermal microvascular endothelial cells express CD32 receptors in vivo and in vitro [17].
  • The highest percentage of CD32 expressing T lymphocytes could be detected after three days of activation [18].
  • Two proteins have been identified on resting human granulocytes which function as Fc gamma receptors, Fc gamma RII (CD32) and Fc gamma RIII (CD16) [19].

Associations of FCGR2B with chemical compounds

  • A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus [13].
  • In cryostat sections of normal human skin, mAb IV.3 or AT10, both recognizing CD32 (Fc gamma RII), localizes to the luminal surface of DMEC of the superficial but not of the deep vascular plexus [17].
  • The expression of Fc gamma RII/CD32 on monocytes was strongly suppressed by calcitriol [20].
  • Fluorescein-or rhodamine-conjugated monoclonal IgG or Fab fragments directed against FcRII (CDw32) and FcRIII (CD16) were employed to label receptors [21].
  • In contrast, the 2.5-kb CDw32 transcript is strongly induced in HL-60 cells which have been induced to differentiate into granulocytes by exposure to dimethylsulfoxide [22].

Regulatory relationships of FCGR2B


Other interactions of FCGR2B

  • HUVEC do not contain Fc gamma RIIa or Fc gamma RIIb mRNA [17].
  • These results suggest that FCGR2B may be deregulated by 1q21 aberration in BCL2 rearranged FLs and possibly play a role in their progression [3].
  • When the present results were combined with our previous data on the Japanese and the Thais using meta-analytic methods, highly significant and independent association was observed for FCGR2B and FCGR3A genotypes [25].
  • Yin-Yang 1 competed with activating protein 1 for binding at the -343 site, and contributed to the repression of the mutant FCGR2B promoter activity [2].
  • The translocation brought the Sgamma2 region of a productive IGH allele 20 approximately 30 kbp upstream of FCGR2B [3].

Analytical, diagnostic and therapeutic context of FCGR2B


  1. A novel polymorphism in the Fcgamma receptor IIB (CD32B) transmembrane region alters receptor signaling. Li, X., Wu, J., Carter, R.H., Edberg, J.C., Su, K., Cooper, G.S., Kimberly, R.P. Arthritis Rheum. (2003) [Pubmed]
  2. The role of activating protein 1 in the transcriptional regulation of the human FCGR2B promoter mediated by the -343 G -> C polymorphism associated with systemic lupus erythematosus. Olferiev, M., Masuda, E., Tanaka, S., Blank, M.C., Pricop, L. J. Biol. Chem. (2007) [Pubmed]
  3. Deregulation of FCGR2B expression by 1q21 rearrangements in follicular lymphomas. Chen, W., Palanisamy, N., Schmidt, H., Teruya-Feldstein, J., Jhanwar, S.C., Zelenetz, A.D., Houldsworth, J., Chaganti, R.S. Oncogene (2001) [Pubmed]
  4. Platelet count, previous infection and FCGR2B genotype predict development of chronic disease in newly diagnosed idiopathic thrombocytopenia in childhood: results of a prospective study. Bruin, M., Bierings, M., Uiterwaal, C., Révész, T., Bode, L., Wiesman, M.E., Kuijpers, T., Tamminga, R., de Haas, M. Br. J. Haematol. (2004) [Pubmed]
  5. A novel human immunoglobulin Fc gamma Fc epsilon bifunctional fusion protein inhibits Fc epsilon RI-mediated degranulation. Zhu, D., Kepley, C.L., Zhang, M., Zhang, K., Saxon, A. Nat. Med. (2002) [Pubmed]
  6. The PI-linked receptor FcRIII is released on stimulation of neutrophils. Huizinga, T.W., van der Schoot, C.E., Jost, C., Klaassen, R., Kleijer, M., von dem Borne, A.E., Roos, D., Tetteroo, P.A. Nature (1988) [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. Functional mapping of the Fc gamma RII binding site on human IgG1 by synthetic peptides. Medgyesi, D., Uray, K., Sallai, K., Hudecz, F., Koncz, G., Abramson, J., Pecht, I., Sármay, G., Gergely, J. Eur. J. Immunol. (2004) [Pubmed]
  9. Phenotypic and functional characterization of a new human macrophage cell line K1m demonstrating immunophagocytic activity and signalling through HLA class II. Dialynas, D.P., Lee, M.J., Shao, L.E., Tan, P.C., Yu, J. Immunology (1997) [Pubmed]
  10. Inhibitory action of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide (PK 11195) on some mononuclear phagocyte functions. Klegeris, A., McGeer, E.G., McGeer, P.L. Biochem. Pharmacol. (2000) [Pubmed]
  11. 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. van Mirre, E., Breunis, W.B., Geissler, J., Hack, C.E., de Boer, M., Roos, D., Kuijpers, T.W. Blood (2006) [Pubmed]
  12. CD72 polymorphisms associated with alternative splicing modify susceptibility to human systemic lupus erythematosus through epistatic interaction with FCGR2B. Hitomi, Y., Tsuchiya, N., Kawasaki, A., Ohashi, J., Suzuki, T., Kyogoku, C., Fukazawa, T., Bejrachandra, S., Siriboonrit, U., Chandanayingyong, D., Suthipinittharm, P., Tsao, B.P., Hashimoto, H., Honda, Z., Tokunaga, K. Hum. Mol. Genet. (2004) [Pubmed]
  13. A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus. Su, K., Wu, J., Edberg, J.C., Li, X., Ferguson, P., Cooper, G.S., Langefeld, C.D., Kimberly, R.P. J. Immunol. (2004) [Pubmed]
  14. 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]
  15. FcgammaRIIB Ile232Thr transmembrane polymorphism associated with human systemic lupus erythematosus decreases affinity to lipid rafts and attenuates inhibitory effects on B cell receptor signaling. Kono, H., Kyogoku, C., Suzuki, T., Tsuchiya, N., Honda, H., Yamamoto, K., Tokunaga, K., Honda, Z. Hum. Mol. Genet. (2005) [Pubmed]
  16. Involvement of the high-affinity receptor for IgG (Fc gamma RI; CD64) in enhanced tumor cell cytotoxicity of neutrophils during granulocyte colony-stimulating factor therapy. Valerius, T., Repp, R., de Wit, T.P., Berthold, S., Platzer, E., Kalden, J.R., Gramatzki, M., van de Winkel, J.G. Blood (1993) [Pubmed]
  17. Dermal microvascular endothelial cells express CD32 receptors in vivo and in vitro. Gröger, M., Sarmay, G., Fiebiger, E., Wolff, K., Petzelbauer, P. J. Immunol. (1996) [Pubmed]
  18. Activation-dependent expression of low affinity IgG receptors Fc gamma RII(CD32) and Fc gamma RIII(CD16) in subpopulations of human T lymphocytes. Engelhardt, W., Matzke, J., Schmidt, R.E. Immunobiology (1995) [Pubmed]
  19. Granulocyte Fc gamma receptor recognition of cell bound and aggregated IgG: effect of gamma-interferon. Ruiz, P., Gomez, F., Lopez, R., Chien, P., Rossman, M.D., Schreiber, A.D. Am. J. Hematol. (1992) [Pubmed]
  20. Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1 alpha,25-dihydroxyvitamin D3 and cytokines. Boltz-Nitulescu, G., Willheim, M., Spittler, A., Leutmezer, F., Tempfer, C., Winkler, S. J. Leukoc. Biol. (1995) [Pubmed]
  21. Cell surface distribution of Fc receptors II and III on living human neutrophils before and during antibody dependent cellular cytotoxicity. Petty, H.R., Francis, J.W., Anderson, C.L. J. Cell. Physiol. (1989) [Pubmed]
  22. Distribution, inducibility and biological function of the cloned and expressed human beta Fc receptor II. Engelhardt, W., Geerds, C., Frey, J. Eur. J. Immunol. (1990) [Pubmed]
  23. Functional regulation of human neutrophil Fc gamma receptors. Selvaraj, P., Fifadara, N., Nagarajan, S., Cimino, A., Wang, G. Immunol. Res. (2004) [Pubmed]
  24. Cooperation between SHP-2, phosphatidyl inositol 3-kinase and phosphoinositol 5-phosphatase in the Fc gamma RIIb mediated B cell regulation. Sármay, G., Koncz, G., Pecht, I., Gergely, J. Immunol. Lett. (1999) [Pubmed]
  25. Association of Fcgamma receptor IIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations. Chu, Z.T., Tsuchiya, N., Kyogoku, C., Ohashi, J., Qian, Y.P., Xu, S.B., Mao, C.Z., Chu, J.Y., Tokunaga, K. Tissue Antigens (2004) [Pubmed]
  26. The Fc receptor for IgG expressed in the villus endothelium of human placenta is Fc gamma RIIb2. Lyden, T.W., Robinson, J.M., Tridandapani, S., Teillaud, J.L., Garber, S.A., Osborne, J.M., Frey, J., Budde, P., Anderson, C.L. J. Immunol. (2001) [Pubmed]
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