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Gene Review

FCGR3B  -  Fc fragment of IgG, low affinity IIIb,...

Homo sapiens

Synonyms: CD16, CD16B, CD16b, FCG3, FCGR3, ...
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Disease relevance of FCGR3B


Psychiatry related information on FCGR3B


High impact information on FCGR3B

  • Mac bound to CD16 (FcgammaRIIIB) on the surface of human polymorphonuclear leukocytes and inhibited opsonophagocytosis and production of reactive oxygen species, which resulted in significantly decreased pathogen killing [7].
  • Efficient internalization and antigen presentation via Fc gamma RIII did not require the cytoplasmic domain of the ligand-binding alpha-chain, but did require the gamma-subunit [8].
  • The structural relatedness of zeta and gamma is emphasized by the recent demonstration of zeta zeta in association with CD16 in TCR-negative natural killer cells [9].
  • Analysis of FcRIII expression in cells of PNH patients, known to be deficient in PI-linked proteins, suggests FcRIII is not PI-linked in monocytes [10].
  • 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 [10].

Chemical compound and disease context of FCGR3B


Biological context of FCGR3B

  • At least one URI was noted in 52% of subjects (99/191) with the NA2/NA2 genotype of the neutrophil-specific FCGR3B gene, compared to 42% (77/181) of those with the NA1/NA2 genotype and 39% (23/59) of those with the NA1/NA1 genotype (P = 0.038) [16].
  • We characterized two FCGR3B cDNAs of different lengths corresponding to two polyadenylation sites [17].
  • This study investigated the FCGR3B gene frequencies and FCGR3 variants in a Chinese population compared with the results of Northern Germans and African Blacks (Uganda) [18].
  • Common polymorphisms have been described in three low-affinity receptors: FCGR2A, FCGR3A, and FCGR3B; each has been shown to alter biological function, and each has also been associated with disease susceptibility [19].
  • The increased association with an FCGR3A-FCGR3B haplotype suggests that other polymorphic variants within FCGR3A or FCGR3B, or in linkage disequilibrium with this haplotype, may additionally contribute to disease pathogenesis [20].

Anatomical context of FCGR3B

  • The FCGR3B chain bears allotypes that define the human neutrophil antigen-1 (HNA-1 and NA) system involved in major post-transfusional reactions [17].
  • FCGR3B is highly homologous to FCGR3A, which is expressed as a transmembrane receptor on natural killer cells and monocytes/macrophages [17].
  • In the present work, we sequenced FCGR3B cDNAs with complete 3' untranslated region from purified granulocytes of HNA-1b/HNA-1b (NA2/NA2) genotyped donors [17].
  • Here, we report that Fc gamma RIII stimulation induces activation of phosphatidylinositol (PI)-3 kinase in NK cells [21].
  • To determine the functional role of the two isoforms of Fc gamma RIII (CD16) (IIIA, IIIB), the signal transduction capabilities of wild-type and mutant forms of these receptors were analyzed in transfected lymphoid, myeloid, and fibroblastic cell lines [22].

Associations of FCGR3B with chemical compounds


Physical interactions of FCGR3B

  • 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 [27].
  • Granulocyte activation via a binding site near the C-terminal region of complement receptor type 3 alpha-chain (CD11b) potentially involved in intramembrane complex formation with glycosylphosphatidylinositol-anchored Fc gamma RIIIB (CD16) molecules [28].

Regulatory relationships of FCGR3B


Other interactions of FCGR3B

  • In addition, the same groups of patients and controls were genotyped for the previously known polymorphisms of FCGR2A, FCGR3A, and FCGR3B [34].
  • Most of the mAbs recognize both the receptor isoforms, transmembranous Fc gamma RIIIA, and glycosylphosphatidylinositol-linked Fc gamma RIIIB [35].
  • Binding epitopes of some of the mAbs that differentiate between the two neutrophil Ag (NA) alleles of Fc gamma RIIIB (CLB-Gran11 against NA1; GRM1, BL-LGL/1 against NA2 allele) have been mapped on the first, membrane-distal domain of CD16 [35].
  • Analysis of Fcgamma receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B [20].
  • Moreover, the expression of HLA-DR molecules by SF macrophages was increased, and the expression of CD16 was decreased by anti-IL-10 MAbs [36].

Analytical, diagnostic and therapeutic context of FCGR3B


  1. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Aitman, T.J., Dong, R., Vyse, T.J., Norsworthy, P.J., Johnson, M.D., Smith, J., Mangion, J., Roberton-Lowe, C., Marshall, A.J., Petretto, E., Hodges, M.D., Bhangal, G., Patel, S.G., Sheehan-Rooney, K., Duda, M., Cook, P.R., Evans, D.J., Domin, J., Flint, J., Boyle, J.J., Pusey, C.D., Cook, H.T. Nature (2006) [Pubmed]
  2. Specificity and class distribution of Fc gamma R-specific autoantibodies in patients with autoimmune disease. Boros, P., Odin, J.A., Chen, J., Unkeless, J.C. J. Immunol. (1994) [Pubmed]
  3. The glycosylphosphatidylinositol-linked Fc gamma receptor III represents the dominant receptor structure for immune complex activation of neutrophils. Hundt, M., Schmidt, R.E. Eur. J. Immunol. (1992) [Pubmed]
  4. Changes of soluble CD16 levels in serum of HIV-infected patients: correlation with clinical and biologic prognostic factors. Khayat, D., Soubrane, C., Andrieu, J.M., Visonneau, S., Eme, D., Tourani, J.M., Beldjord, K., Weil, M., Fernandez, E., Jacquillat, C. J. Infect. Dis. (1990) [Pubmed]
  5. Circulating lymphocyte phenotypic surface markers in anxiety disorder patients and normal volunteers. Rapaport, M.H. Biol. Psychiatry (1998) [Pubmed]
  6. Impairment of neutrophil Fc gamma receptor mediated transmembrane signalling in active rheumatoid arthritis. Goulding, N.J., Guyre, P.M. Ann. Rheum. Dis. (1992) [Pubmed]
  7. Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis. Lei, B., DeLeo, F.R., Hoe, N.P., Graham, M.R., Mackie, S.M., Cole, R.L., Liu, M., Hill, H.R., Low, D.E., Federle, M.J., Scott, J.R., Musser, J.M. Nat. Med. (2001) [Pubmed]
  8. Tyrosine-containing motif that transduces cell activation signals also determines internalization and antigen presentation via type III receptors for IgG. Amigorena, S., Salamero, J., Davoust, J., Fridman, W.H., Bonnerot, C. Nature (1992) [Pubmed]
  9. Family of disulphide-linked dimers containing the zeta and eta chains of the T-cell receptor and the gamma chain of Fc receptors. Orloff, D.G., Ra, C.S., Frank, S.J., Klausner, R.D., Kinet, J.P. Nature (1990) [Pubmed]
  10. 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]
  11. Alloimmune neonatal neutropenia due to an antibody to the neutrophil Fc-gamma receptor III with maternal deficiency of CD16 antigen. Stroncek, D.F., Skubitz, K.M., Plachta, L.B., Shankar, R.A., Clay, M.E., Herman, J., Fleit, H.B., McCullough, J. Blood (1991) [Pubmed]
  12. In vitro packaging of an infectious recombinant adeno-associated virus 2. Ding, L., Lu, S., Munshi, N.C. Gene Ther. (1997) [Pubmed]
  13. Expression of CD14, CD16 and CD45RA on monocytes from periodontitis patients. Nagasawa, T., Kobayashi, H., Aramaki, M., Kiji, M., Oda, S., Izumi, Y. J. Periodont. Res. (2004) [Pubmed]
  14. Polymorphonuclear leukocyte opsonic receptor expression after hypoxia/reoxygenation. Simms, H., D'Amico, R., Garner, C. J. Lab. Clin. Med. (1996) [Pubmed]
  15. Modulation of human leukocyte antigen-DR on monocytes and CD16 on granulocytes in patients with septic shock using hemoperfusion with polymyxin B-immobilized fiber. Ono, S., Tsujimoto, H., Matsumoto, A., Ikuta, S., Kinoshita, M., Mochizuki, H. Am. J. Surg. (2004) [Pubmed]
  16. Genetic risk factors for infection in patients with early rheumatoid arthritis. Hughes, L.B., Criswell, L.A., Beasley, T.M., Edberg, J.C., Kimberly, R.P., Moreland, L.W., Seldin, M.F., Bridges, S.L. Genes Immun. (2004) [Pubmed]
  17. Characterization of human FCGR3B*02 (HNA-1b, NA2) cDNAs and IMGT standardized description of FCGR3B alleles. Bertrand, G., Duprat, E., Lefranc, M.P., Marti, J., Coste, J. Tissue Antigens (2004) [Pubmed]
  18. FCGR3B gene frequencies and FCGR3 variants in a Chinese population from Zhejiang Province. Tong, Y., Jin, J., Yan, L., Neppert, J., Marget, M., Flesch, B.K. Ann. Hematol. (2003) [Pubmed]
  19. Patterns of low-affinity immunoglobulin receptor polymorphisms in stroke and homozygous sickle cell disease. Taylor, J.G., Tang, D., Foster, C.B., Serjeant, G.R., Rodgers, G.P., Chanock, S.J. Am. J. Hematol. (2002) [Pubmed]
  20. Analysis of Fcgamma receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B. Morgan, A.W., Barrett, J.H., Griffiths, B., Subramanian, D., Robinson, J.I., Keyte, V.H., Ali, M., Jones, E.A., Old, R.W., Ponchel, F., Boylston, A.W., Situnayake, R.D., Markham, A.F., Emery, P., Isaacs, J.D. Arthritis Res. Ther. (2006) [Pubmed]
  21. Phosphatidylinositol-3 kinase activation induced upon Fc gamma RIIIA-ligand interaction. Kanakaraj, P., Duckworth, B., Azzoni, L., Kamoun, M., Cantley, L.C., Perussia, B. J. Exp. Med. (1994) [Pubmed]
  22. Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain. Wirthmueller, U., Kurosaki, T., Murakami, M.S., Ravetch, J.V. J. Exp. Med. (1992) [Pubmed]
  23. Physical and functional association of p56lck with Fc gamma RIIIA (CD16) in natural killer cells. Salcedo, T.W., Kurosaki, T., Kanakaraj, P., Ravetch, J.V., Perussia, B. J. Exp. Med. (1993) [Pubmed]
  24. Soluble Fc gamma RIIIa is present in plasma and is derived from natural killer cells. de Haas, M., Kleijer, M., Minchinton, R.M., Roos, D., von dem Borne, A.E. J. Immunol. (1994) [Pubmed]
  25. Binding of monomeric human IgG defines an expression polymorphism of Fc gamma RIII on large granular lymphocyte/natural killer cells. Vance, B.A., Huizinga, T.W., Wardwell, K., Guyre, P.M. J. Immunol. (1993) [Pubmed]
  26. Human neutrophil Fc gamma RIIIB and formyl peptide receptors are functionally linked during formyl-methionyl-leucyl-phenylalanine-induced chemotaxis. Kew, R.R., Grimaldi, C.M., Furie, M.B., Fleit, H.B. J. Immunol. (1992) [Pubmed]
  27. 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]
  28. Granulocyte activation via a binding site near the C-terminal region of complement receptor type 3 alpha-chain (CD11b) potentially involved in intramembrane complex formation with glycosylphosphatidylinositol-anchored Fc gamma RIIIB (CD16) molecules. Stöckl, J., Majdic, O., Pickl, W.F., Rosenkranz, A., Prager, E., Gschwantler, E., Knapp, W. J. Immunol. (1995) [Pubmed]
  29. Regulation of production of soluble Fc gamma receptors type III in normal and pathological conditions. Moldovan, I., Galon, J., Maridonneau-Parini, I., Roman Roman, S., Mathiot, C., Fridman, W.H., Sautès-Fridman, C. Immunol. Lett. (1999) [Pubmed]
  30. Expression of FcgammaRIII (CD16) on human peripheral blood eosinophils increases in allergic conditions. Davoine, F., Lavigne, S., Chakir, J., Ferland, C., Boulay, M.E., Laviolette, M. J. Allergy Clin. Immunol. (2002) [Pubmed]
  31. Reactive oxygen intermediates enhance Fc gamma receptor signaling and amplify phagocytic capacity. Pricop, L., Gokhale, J., Redecha, P., Ng, S.C., Salmon, J.E. J. Immunol. (1999) [Pubmed]
  32. Granulocyte-macrophage colony-stimulating factor antagonizes the transforming growth factor-beta-induced expression of Fc gamma RIII (CD16) on human monocytes. Kruger, M., Coorevits, L., De Wit, T.P., Casteels-Van Daele, M., Van De Winkel, J.G., Ceuppens, J.L. Immunology (1996) [Pubmed]
  33. Activation of human neutrophils by soluble immune complexes: role of Fc gamma RII and Fc gamma RIIIb in stimulation of the respiratory burst and elevation of intracellular Ca2+. Edwards, S.W., Watson, F., Gasmi, L., Moulding, D.A., Quayle, J.A. Ann. N. Y. Acad. Sci. (1997) [Pubmed]
  34. 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]
  35. The binding epitopes of human CD16 (Fc gamma RIII) monoclonal antibodies. Implications for ligand binding. Tamm, A., Schmidt, R.E. J. Immunol. (1996) [Pubmed]
  36. Interleukin-10 functions as an antiinflammatory cytokine in rheumatoid synovium. Isomaki, P., Luukkainen, R., Saario, R., Toivanen, P., Punnonen, J. Arthritis Rheum. (1996) [Pubmed]
  37. Intracellular expression of Fc gamma RIII (CD16) and its mobilization by chemoattractants in human eosinophils. Zhu, X., Hamann, K.J., Muñoz, N.M., Rubio, N., Mayer, D., Hernrreiter, A., Leff, A.R. J. Immunol. (1998) [Pubmed]
  38. Abnormal neutrophil phenotype and neutrophil FcRIII deficiency corrected by bone marrow transplantation. Minchinton, R.M., de Haas, M., von dem Borne, A.E., Kleijer, M., Roberts, A.W., Gillett, E.A. Transfusion (1995) [Pubmed]
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