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Gene Review

Fcgr2b  -  Fc receptor, IgG, low affinity IIb

Mus musculus

Synonyms: AI528646, CD32, F630109E10Rik, Fc gamma RIIB, Fc gamma receptor IIB, ...
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Disease relevance of Fcgr2b


Psychiatry related information on Fcgr2b

  • CTC cells originating from tumors which appeared after a long latency period (late tumors) tended to express Fc gamma RII while CTC cells originating from tumors which appeared after a short latency period (early tumors) as well as the corresponding C cells tended not to express Fc gamma RII [4].
  • Furthermore, by using knockout mice, we have shown that inhibition of the Id-specific memory B cells by the Id protein is largely independent of the FcgammaRIIB and, hence, independent of immune complexes [5].

High impact information on Fcgr2b

  • A population of early fetal thymocytes expressing Fc gamma RII/III contains precursors of T lymphocytes and natural killer cells [6].
  • Our results show that this chimeric protein is able to form complexes with both Fc epsilon RI and Fc gamma RII, and inhibit mast-cell and basophil function [7].
  • Mouse monoclonal antibodies, as well as the humanized, clinically effective therapeutic agents trastuzumab (Herceptin(R)) and rituximab (Rituxan(R)), engaged both activation (FcgammaRIII) and inhibitory (FcgammaRIIB) antibody receptors on myeloid cells, thus modulating their cytotoxic potential [8].
  • These results demonstrate that Fc-receptor-dependent mechanisms contribute substantially to the action of cytotoxic antibodies against tumors and indicate that an optimal antibody against tumors would bind preferentially to activation Fc receptors and minimally to the inhibitory partner FcgammaRIIB [8].
  • Crosslinking Fc gamma RIIB with the surface immunoglobulin complex confers a dominant signal that prevents or aborts lymphocyte activation triggered through the ARH-1 motifs of the signal transduction subunits Ig-alpha and Ig-beta [9].

Chemical compound and disease context of Fcgr2b


Biological context of Fcgr2b


Anatomical context of Fcgr2b


Associations of Fcgr2b with chemical compounds

  • In addition to facilitating the recruitment of SHIPs, the second tyrosine-based motif may confer upon FcgammaRIIB the properties of scaffold proteins capable of altering the composition and stability of the signaling complexes generated following receptor engagement [20].
  • When coaggregated with ITAM-bearing receptors, FcgammaRIIB become tyrosyl-phosphorylated and recruit the Src homology 2 (SH2) domain-containing inositol 5'-phosphatases SHIP1 and SHIP2, which mediate inhibition [20].
  • To test this possibility, we determined the development of RF in C57BL/6 (B6) mice lacking FcgammaRIIB, in relation to the H2 haplotype, complement C3, and the Y-linked autoimmune acceleration (Yaa) mutation [21].
  • Tumor necrosis factor induces a block in the cotranslation of Fc gamma RIIb mRNA in mouse peritoneal macrophages [22].
  • In contrast to the lymphoid precursors, myeloid precursors able to generate colonies in methyl cellulose cultures were found in all four fractions including the one which expressed Fc gamma RII/III but no AA4.1 (FcR+) and the one which expressed neither marker (AA4.1-/FcR-) [23].

Physical interactions of Fcgr2b


Regulatory relationships of Fcgr2b

  • Chondrocyte death was reduced in Fc gamma RIII(-/-) mice (68% lower) and enhanced in Fc gamma RII(-/-) mice (6-12-fold higher) [29].
  • Crosslinking of Fc gamma RII induced a rapid increase in the tyrosine kinase activity and comodulation of Fgr [30].
  • Alternatively, homoaggregation of FcgammaRIIB can induce a proapoptotic state in B cells that is dependent on the presence of Bruton tyrosine kinase (Btk), a kinase also expressed in monocytes [31].
  • In contrast, absence of the inhibiting FcgammaRIIB augmented the Hg-induced increase of both serum IgG1 and IgE [32].
  • Previous studies by our lab and others established that co-crosslinking sIg and IgG receptor FcgammaRIIb in B cells in a feedback suppression model (negative signaling) promoted tyrosine phosphorylation of the inositol 5-phosphatase SHIP and its interaction with Shc and that these events were associated with inhibition of the Ras pathway [33].

Other interactions of Fcgr2b


Analytical, diagnostic and therapeutic context of Fcgr2b


  1. Genetic modifiers of systemic lupus erythematosus in FcgammaRIIB(-/-) mice. Bolland, S., Yim, Y.S., Tus, K., Wakeland, E.K., Ravetch, J.V. J. Exp. Med. (2002) [Pubmed]
  2. Fc gamma Rs modulate cytotoxicity of anti-Fas antibodies: implications for agonistic antibody-based therapeutics. Xu, Y., Szalai, A.J., Zhou, T., Zinn, K.R., Chaudhuri, T.R., Li, X., Koopman, W.J., Kimberly, R.P. J. Immunol. (2003) [Pubmed]
  3. FcgammaRIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune disease. Yajima, K., Nakamura, A., Sugahara, A., Takai, T. Eur. J. Immunol. (2003) [Pubmed]
  4. Phenotypic properties of 3T3 cells transformed in vitro with polyoma virus and passaged once in syngeneic animals. Langer, A.B., Emmanuel, N., Even, J., Fridman, W.H., Gohar, O., Gonen, B., Katz, B.Z., Ran, M., Smorodinsky, N.I., Witz, I.P. Immunobiology (1992) [Pubmed]
  5. Inhibition of a vaccine-induced anti-tumor B cell response by soluble protein antigen in the absence of continuing T cell help. Savelyeva, N., King, C.A., Vitetta, E.S., Stevenson, F.K. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. A population of early fetal thymocytes expressing Fc gamma RII/III contains precursors of T lymphocytes and natural killer cells. Rodewald, H.R., Moingeon, P., Lucich, J.L., Dosiou, C., Lopez, P., Reinherz, E.L. Cell (1992) [Pubmed]
  7. 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]
  8. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Clynes, R.A., Towers, T.L., Presta, L.G., Ravetch, J.V. Nat. Med. (2000) [Pubmed]
  9. A 13-amino-acid motif in the cytoplasmic domain of Fc gamma RIIB modulates B-cell receptor signalling. Muta, T., Kurosaki, T., Misulovin, Z., Sanchez, M., Nussenzweig, M.C., Ravetch, J.V. Nature (1994) [Pubmed]
  10. Potentiation of antiproliferative effects of monoclonal antibody Lym-1 and immunoconjugate Lym-1-gelonin on human Burkitt's lymphoma cells with gamma-interferon and tumor necrosis factor. O'Boyle, K.P., Colletti, D., Mazurek, C., Wang, Y., Ray, S.K., Diamond, B., Rosenblum, M.G., Epstein, A.L., Shochat, D., Dutcher, J.P. Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy. (1995) [Pubmed]
  11. Cross-linking of IgG receptors inhibits membrane immunoglobulin-stimulated calcium influx in B lymphocytes. Choquet, D., Partiseti, M., Amigorena, S., Bonnerot, C., Fridman, W.H., Korn, H. J. Cell Biol. (1993) [Pubmed]
  12. Maximum-tolerated dose, toxicity, and efficacy of (131)I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma. DeNardo, G.L., DeNardo, S.J., Goldstein, D.S., Kroger, L.A., Lamborn, K.R., Levy, N.B., McGahan, J.P., Salako, Q., Shen, S., Lewis, J.P. J. Clin. Oncol. (1998) [Pubmed]
  13. Characterization of anti-mouse Fc gamma RII single-chain Fv fragments derived from human phage display libraries. McCall, A.M., Amoroso, A.R., Sautès, C., Marks, J.D., Weiner, L.M. Immunotechnology (1998) [Pubmed]
  14. Contribution of NZB autoimmunity 2 to Y-linked autoimmune acceleration-induced monocytosis in association with murine systemic lupus. Kikuchi, S., Santiago-Raber, M.L., Amano, H., Amano, E., Fossati-Jimack, L., Moll, T., Kotzin, B.L., Izui, S. J. Immunol. (2006) [Pubmed]
  15. Transcriptional regulation of Fcgr2b gene by polymorphic promoter region and its contribution to humoral immune responses. Xiu, Y., Nakamura, K., Abe, M., Li, N., Wen, X.S., Jiang, Y., Zhang, D., Tsurui, H., Matsuoka, S., Hamano, Y., Fujii, H., Ono, M., Takai, T., Shimokawa, T., Ra, C., Shirai, T., Hirose, S. J. Immunol. (2002) [Pubmed]
  16. B lymphocyte memory: role of stromal cell complement and FcgammaRIIB receptors. Barrington, R.A., Pozdnyakova, O., Zafari, M.R., Benjamin, C.D., Carroll, M.C. J. Exp. Med. (2002) [Pubmed]
  17. Fc gammaRII (CD32) is linked to apoptotic pathways in murine granulocyte precursors and mature eosinophils. de Andrés, B., Mueller, A.L., Blum, A., Weinstock, J., Verbeek, S., Sandor, M., Lynch, R.G. Blood (1997) [Pubmed]
  18. Regulated expression and inhibitory function of Fcgamma RIIb in human monocytic cells. Tridandapani, S., Siefker, K., Teillaud, J.L., Carter, J.E., Wewers, M.D., Anderson, C.L. J. Biol. Chem. (2002) [Pubmed]
  19. Antibody isotype-specific engagement of Fcgamma receptors regulates B lymphocyte depletion during CD20 immunotherapy. Hamaguchi, Y., Xiu, Y., Komura, K., Nimmerjahn, F., Tedder, T.F. J. Exp. Med. (2006) [Pubmed]
  20. Two distinct tyrosine-based motifs enable the inhibitory receptor FcgammaRIIB to cooperatively recruit the inositol phosphatases SHIP1/2 and the adapters Grb2/Grap. Isnardi, I., Lesourne, R., Bruhns, P., Fridman, W.H., Cambier, J.C., Daëron, M. J. Biol. Chem. (2004) [Pubmed]
  21. A critical role for Fc gamma RIIB in the induction of rheumatoid factors. Moll, T., Nitschke, L., Carroll, M., Ravetch, J.V., Izui, S. J. Immunol. (2004) [Pubmed]
  22. Tumor necrosis factor induces a block in the cotranslation of Fc gamma RIIb mRNA in mouse peritoneal macrophages. Chicheportiche, Y., Vassalli, P. J. Biol. Chem. (1994) [Pubmed]
  23. Expression of Fc gamma RIII defines distinct subpopulations of fetal liver B cell and myeloid precursors. Carlsson, L., Candéias, S., Staerz, U., Keller, G. Eur. J. Immunol. (1995) [Pubmed]
  24. Molecular cloning and expression of the mouse high affinity Fc receptor for IgG. Sears, D.W., Osman, N., Tate, B., McKenzie, I.F., Hogarth, P.M. J. Immunol. (1990) [Pubmed]
  25. Proteolysis induces increased binding affinity of the monocyte type II FcR for human IgG. van de Winkel, J.G., van Ommen, R., Huizinga, T.W., de Raad, M.A., Tuijnman, W.B., Groenen, P.J., Capel, P.J., Koene, R.A., Tax, W.J. J. Immunol. (1989) [Pubmed]
  26. Dynamic interactions of Fc gamma receptor IIB with filamin-bound SHIP1 amplify filamentous actin-dependent negative regulation of Fc epsilon receptor I signaling. Lesourne, R., Fridman, W.H., Daëron, M. J. Immunol. (2005) [Pubmed]
  27. Unique features of SHIP, SHP-1 and SHP-2 binding to FcgammaRIIb revealed by surface plasmon resonance analysis. Famiglietti, S.J., Nakamura, K., Cambier, J.C. Immunol. Lett. (1999) [Pubmed]
  28. Two distinct regions of the mouse beta Fc gamma R gene control its transcription. Bonnerot, C., Choukroun, V., Marloie, M.A., Fridman, W.H. Immunobiology (1992) [Pubmed]
  29. Coordinate expression of activating Fc gamma receptors I and III and inhibiting Fc gamma receptor type II in the determination of joint inflammation and cartilage destruction during immune complex-mediated arthritis. Nabbe, K.C., Blom, A.B., Holthuysen, A.E., Boross, P., Roth, J., Verbeek, S., van Lent, P.L., van den Berg, W.B. Arthritis Rheum. (2003) [Pubmed]
  30. Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils. Hamada, F., Aoki, M., Akiyama, T., Toyoshima, K. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  31. IVIg-mediated amelioration of murine ITP via FcgammaRIIB is independent of SHIP1, SHP-1, and Btk activity. Crow, A.R., Song, S., Freedman, J., Helgason, C.D., Humphries, R.K., Siminovitch, K.A., Lazarus, A.H. Blood (2003) [Pubmed]
  32. The role of Fc-receptors in murine mercury-induced systemic autoimmunity. Martinsson, K., Hultman, P. Clin. Exp. Immunol. (2006) [Pubmed]
  33. Role of SHIP in FcgammaRIIb-mediated inhibition of Ras activation in B cells. Tridandapani, S., Phee, H., Shivakumar, L., Kelley, T.W., Coggeshall, K.M. Mol. Immunol. (1998) [Pubmed]
  34. Induction of intracellular Ca2+ mobilization and cytotoxicity by hybrid mouse monoclonal antibodies. Fc gamma RII regulation of Fc gamma RI-triggered functions or signaling? Koolwijk, P., Van de Winkel, J.G., Pfefferkorn, L.C., Jacobs, C.W., Otten, I., Spierenburg, G.T., Bast, B.J. J. Immunol. (1991) [Pubmed]
  35. Src homology 2 domain-containing inositol 5-phosphatase 1 mediates cell cycle arrest by FcgammaRIIB. Malbec, O., Schmitt, C., Bruhns, P., Krystal, G., Fridman, W.H., Daëron, M. J. Biol. Chem. (2001) [Pubmed]
  36. IgG-mediated enhancement of antibody responses is low in Fc receptor gamma chain-deficient mice and increased in Fc gamma RII-deficient mice. Wernersson, S., Karlsson, M.C., Dahlström, J., Mattsson, R., Verbeek, J.S., Heyman, B. J. Immunol. (1999) [Pubmed]
  37. Fc gamma RIIB regulates nasal and oral tolerance: a role for dendritic cells. Samsom, J.N., van Berkel, L.A., van Helvoort, J.M., Unger, W.W., Jansen, W., Thepen, T., Mebius, R.E., Verbeek, S.S., Kraal, G. J. Immunol. (2005) [Pubmed]
  38. A new set of monoclonal antibodies against human Fc gamma RII (CD32) and Fc gamma RIII (CD16): characterization and use in various assays. Vely, F., Gruel, N., Moncuit, J., Cochet, O., Rouard, H., Dare, S., Galon, J., Sautes, C., Fridman, W.H., Teillaud, J.L. Hybridoma (1997) [Pubmed]
  39. Ontogeny and distribution of the murine B cell Fc gamma RII. Foy, T.M., Lynch, R.G., Waldschmidt, T.J. J. Immunol. (1992) [Pubmed]
  40. Biochemical characterization of murine lymphoid alloantigen Ly-m20.2, a cell surface marker controlled by a gene linked to the Mls locus. Mark, W.H., Kimura, S., Hämmerling, U. J. Immunol. (1985) [Pubmed]
  41. Differential expression of the inhibitory IgG Fc receptor FcgammaRIIB on germinal center cells: implications for selection of high-affinity B cells. Rao, S.P., Vora, K.A., Manser, T. J. Immunol. (2002) [Pubmed]
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