FCGR2B
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| Location (UCSC) | Chr 1: 161.66 – 161.68 Mb | Chr 1: 170.79 – 170.8 Mb | |||||||
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Fc fragment of IgG receptor IIb (coded by FCGR2B gene) is a
Structure
There are two major forms of FCGR2B existing (FCGR2B1 and FCGR2B2) and they are created by mRNA splicing mechanism, which results in the inclusion (FCGR2B1) or exclusion (FCGR2B2) of the C1
Expression
FCGR2B1 is highly expressed by B cells, and its mRNA has also been identified at lower levels on
FCGR2B is co-expressed with the activating FCGRA on circulating myeloid dendritic cells.[8]
Function
The receptor inhibits the functions of activating FcγRs, such as phagocytosis and pro-inflammatory cytokine release, mainly by clustering of FCGR2B with different activating FCGR receptors or with the BCR by immune complexes.[9][6]
The phosphorylated ITIM of FcγRIIB recruits the inositol
FCGR2B regulates B cell activation by increasing the BCR activation threshold and suppressing B cell-mediated antigen presentation to T cells through the ITIM-dependent inhibitory mechanism.[9] Ligation of FCGR2B on B cells downregulates antibody production, prevents the membrane organization of BCR and CD19 and promotes apoptosis. Co-ligation of FCGR2B on dendritic cells inhibits maturation and blocks cell activation.[6][8] The negative regulatory role of the FCGRIIB molecule is not limited to BCR-induced B-cell activation, but is also functional on other B-cell activation pathways mediated by CD40 and IL-4.[11] BCR signaling attenuates the pro-apoptotic signaling induced by aggregation of FcγRIIB through immune complexes,[12] allowing for FcγRIIB to effectively tune the affinity threshold for antigen in immune responses and selectively promote retention and survival of high-affinity B cells.[13]
The transmembrane region of FcγRIIB also appears to be functionally important.
FCGR2B expression on follicular dendritic cells (FDCs) is important for capturing the antigen-containing immune complexes which are essential for the germinal centre response.[9] It has been shown that in the absence of FcγRIIB on FDCs, the germinal centers are more diverse but populated by low affinity B cells with low levels of somatic hypermutation.[15] The mechanisms underlying this are incompletely understood, but it is noted that the ability of FDCs to retain immune complexes in the absence of FcγRIIB is impaired and this may result in lower stringency in selection for entry into the germinal center reaction.
FCGR2B is present on non-leukocyte cells including airway smooth muscle and liver sinusoidal endothelial cells, where small immune complexes are internalized inhibiting the pro-inflammatory signalling.[6]
Autoimmunity
FCGR2B is one of the genes thought to influence susceptibility to several autoimmune diseases in humans. Its decreased function is associated with
FCGR2B may be a target for monoclonal antibody therapy for autoimmune diseases as well as malignancies.[9][16][17]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000072694 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026656 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "FCGR2B Fc fragment of IgG receptor IIb [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-06-14.
- ^ PMID 30941127.
- PMID 25045879.
- ^ PMID 16167082.
- ^ PMID 20414206.
- PMID 35858562.
- PMID 15946258.
- PMID 10403650.
- PMID 31478910.
- PMID 29497990.
- PMID 31775042.
- PMID 16757681.
- PMID 18216299.
Further reading
- Tsuchiya N, Kyogoku C (August 2005). "Role of Fc gamma receptor IIb polymorphism in the genetic background of systemic lupus erythematosus: insights from Asia". Autoimmunity. 38 (5): 347–352. S2CID 37295376.
- Engelhardt W, Geerds C, Frey J (June 1990). "Distribution, inducibility and biological function of the cloned and expressed human beta Fc receptor II". European Journal of Immunology. 20 (6): 1367–1377. S2CID 13498051.
- Seki T (1989). "Identification of multiple isoforms of the low-affinity human IgG Fc receptor". Immunogenetics. 30 (1): 5–12. S2CID 23208039.
- Brooks DG, Qiu WQ, Luster AD, Ravetch JV (October 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. 170 (4): 1369–1385. PMID 2529342.
- Stuart SG, Simister NE, Clarkson SB, Kacinski BM, Shapiro M, Mellman I (December 1989). "Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium". The EMBO Journal. 8 (12): 3657–3666. PMID 2531080.
- Stengelin S, Stamenkovic I, Seed B (April 1988). "Isolation of cDNAs for two distinct human Fc receptors by ligand affinity cloning". The EMBO Journal. 7 (4): 1053–1059. PMID 3402431.
- Engelhardt W, Matzke J, Schmidt RE (April 1995). "Activation-dependent expression of low affinity IgG receptors Fc gamma RII(CD32) and Fc gamma RIII(CD16) in subpopulations of human T lymphocytes". Immunobiology. 192 (5): 297–320. PMID 7649565.
- D'Ambrosio D, Hippen KL, Minskoff SA, Mellman I, Pani G, Siminovitch KA, Cambier JC (April 1995). "Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by Fc gamma RIIB1". Science. 268 (5208): 293–297. PMID 7716523.
- Warmerdam PA, van den Herik-Oudijk IE, Parren PW, Westerdaal NA, van de Winkel JG, Capel PJ (March 1993). "Interaction of a human Fc gamma RIIb1 (CD32) isoform with murine and human IgG subclasses". International Immunology. 5 (3): 239–247. PMID 8466861.
- Bewarder N, Weinrich V, Budde P, Hartmann D, Flaswinkel H, Reth M, Frey J (September 1996). "In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcgammaRII) phosphorylation". Molecular and Cellular Biology. 16 (9): 4735–4743. PMID 8756631.
- Sandilands GP, MacPherson SA, Burnett ER, Russell AJ, Downie I, MacSween RN (June 1997). "Differential expression of CD32 isoforms following alloactivation of human T cells". Immunology. 91 (2): 204–211. PMID 9227318.
- De SK, Venkateshan CN, Seth P, Gajdusek DC, Gibbs CJ (March 1998). "Adenovirus-mediated human immunodeficiency virus-1 Nef expression in human monocytes/macrophages and effect of Nef on downmodulation of Fcgamma receptors and expression of monokines". Blood. 91 (6): 2108–2117. PMID 9490697.
- Metes D, Ernst LK, Chambers WH, Sulica A, Herberman RB, Morel PA (April 1998). "Expression of functional CD32 molecules on human NK cells is determined by an allelic polymorphism of the FcgammaRIIC gene". Blood. 91 (7): 2369–2380. PMID 9516136.
- Sondermann P, Huber R, Jacob U (March 1999). "Crystal structure of the soluble form of the human fcgamma-receptor IIb: a new member of the immunoglobulin superfamily at 1.7 A resolution". The EMBO Journal. 18 (5): 1095–1103. PMID 10064577.
- Muraille E, Bruhns P, Pesesse X, Daëron M, Erneux C (April 2000). "The SH2 domain containing inositol 5-phosphatase SHIP2 associates to the immunoreceptor tyrosine-based inhibition motif of Fc gammaRIIB in B cells under negative signaling". Immunology Letters. 72 (1): 7–15. PMID 10789675.
- Pricop L, Redecha P, Teillaud JL, Frey J, Fridman WH, Sautès-Fridman C, Salmon JE (January 2001). "Differential modulation of stimulatory and inhibitory Fc gamma receptors on human monocytes by Th1 and Th2 cytokines". Journal of Immunology. 166 (1): 531–537. PMID 11123333.
- Lyden TW, Robinson JM, Tridandapani S, Teillaud JL, Garber SA, Osborne JM, et al. (March 2001). "The Fc receptor for IgG expressed in the villus endothelium of human placenta is Fc gamma RIIb2". Journal of Immunology. 166 (6): 3882–3889. PMID 11238632.
- Bharadwaj D, Mold C, Markham E, Du Clos TW (June 2001). "Serum amyloid P component binds to Fc gamma receptors and opsonizes particles for phagocytosis". Journal of Immunology. 166 (11): 6735–6741. PMID 11359830.
- Jessup CF, Ridings J, Ho A, Nobbs S, Roberton DM, Macardle P, Zola H (July 2001). "The Fc receptor for IgG (Fc gamma RII; CD32) on human neonatal B lymphocytes". Human Immunology. 62 (7): 679–685. PMID 11423173.
External links
- FCGR2B+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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