FCGR2B

FCGR2B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2FCB, 3WJJ,%%s3WJL
Identifiers
Aliases	FCGR2B, CD32, CD32B, FCG2, FCGR2, IGFR2, Fc fragment of IgG receptor IIb, FcRII-c, FCGR2C
External IDs	OMIM: 604590; MGI: 95499; HomoloGene: 2974; GeneCards: FCGR2B; OMA:FCGR2B - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q23.3 Start 161,663,147 bp[1] End 161,678,654 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 H3|1 78.02 cM Start 170,786,186 bp[2] End 170,804,116 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in placenta right coronary artery blood spleen monocyte lymph node synovial membrane synovial joint granulocyte appendix Top expressed in stroma of bone marrow tibiofemoral joint calvaria granulocyte skin of abdomen blood spleen right kidney molar motor neuron More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding IgG binding amyloid-beta binding low-affinity IgG receptor activity protein-containing complex binding transmembrane signaling receptor activity Cellular component integral component of membrane plasma membrane membrane integral component of plasma membrane external side of plasma membrane dendritic spine cell body cytoplasm Biological process viral process immune response signal transduction regulation of immune response negative regulation of type I hypersensitivity negative regulation of antibody-dependent cellular cytotoxicity follicular dendritic cell activation mature B cell differentiation involved in immune response follicular B cell differentiation immune complex clearance by monocytes and macrophages negative regulation of dendritic cell antigen processing and presentation regulation of B cell antigen processing and presentation negative regulation of immunoglobulin production regulation of adaptive immune response negative regulation of acute inflammatory response to antigenic stimulus positive regulation of humoral immune response negative regulation of humoral immune response mediated by circulating immunoglobulin receptor-mediated endocytosis phagocytosis, engulfment defense response inflammatory response response to bacterium regulation of signaling receptor activity immunoglobulin mediated immune response antigen processing and presentation of exogenous peptide antigen via MHC class II cerebellum development negative regulation of B cell proliferation negative regulation of interleukin-10 production Fc-gamma receptor signaling pathway involved in phagocytosis negative regulation of macrophage activation negative regulation of cytotoxic T cell degranulation regulation of innate immune response mast cell activation positive regulation of JNK cascade negative regulation of phagocytosis positive regulation of phagocytosis negative regulation of immune response negative regulation of B cell receptor signaling pathway negative regulation of B cell activation cellular response to molecule of bacterial origin regulation of immune complex clearance by monocytes and macrophages positive regulation of neuron death negative regulation of neutrophil activation regulation of dendritic spine maintenance cellular response to amyloid-beta positive regulation of response to endoplasmic reticulum stress negative regulation of dendritic cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2213 14130 Ensembl ENSG00000072694 ENSMUSG00000026656 UniProt P31994 P31995 P08101 RefSeq (mRNA) NM_001002273 NM_001002274 NM_001002275 NM_001190828 NM_004001 NM_001077189 NM_010187 RefSeq (protein) NP_001002273 NP_001002274 NP_001002275 NP_001177757 NP_003992 NP_963857 NP_001070657 NP_034317 Location (UCSC) Chr 1: 161.66 – 161.68 Mb Chr 1: 170.79 – 170.8 Mb PubMed search [3] [4]
Wikidata
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Fc fragment of IgG receptor IIb (coded by FCGR2B gene) is a low affinity inhibitory receptor for the Fc region of immunoglobulin gamma (IgG). FCGR2B participates in the phagocytosis of immune complexes and in the regulation of antibody production by B lymphocytes.^[5]

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 exon sequence. The presence of the C1 exon sequence (in FCGR2B1) results in tethering to the membrane of B cells, whereas its absence (in FCGR2B2) allows fast internalization of the receptor in myeloid cells. Both forms contain the Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) in their cytoplasmic regions. The extracellular domains are 95% identical to the domains of FCGR2A and almost completely identical to the FCGR2C (the other members of CD32 family).^[6] It is the only inhibitory type I FcγR^[7] in humans and mice.

Expression

FCGR2B1 is highly expressed by B cells, and its mRNA has also been identified at lower levels on monocytes. FCGR2B2 is highly expressed on basophils and at low levels on monocytes. FCGR2B is co-expressed with the activating FCGRA on circulating myeloid dendritic cells in peripheral blood.^[8] Cytokine regulation of the expression is positive in the case of IL-10 and IL-6 and negative in the case of TNF-α, C5a and IFN-γ.^[6]

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 phosphatases SHIP1 and SHIP2, which inhibit Ras activation, downregulate MAPK activity and reduce PLCγ function and lead to decreased activation of PKC. Inhibition of the MAP kinase pathway, together with the anti-apoptotic kinase Akt can negatively affect proliferation and survival of the cells.^[6] However, FcγRIIB can restrict activation of cells bearing FcγRs by simply competing with them for engagement with immune complexes, as removal of the ITIM retains this activity.^[10]

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.^[14] Multiple epidemiological studies link polymorphisms in the transmembrane domain of FcγRIIB to autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis. Mutagenesis studies confirm that lesioning the transmembrane region impairs the ability of FcγRIIB to attenuate B cell signaling. Multiple mechanisms are proposed to account for this, relating to the ability of FcγRIIB to co-localize with the BCR, colocalize with activating FcγRs (in non-B cells), prevent its colocalization with the activating receptor CD19.

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 systemic lupus erythematosus, rheumatoid arthritis, Goodpasture's disease, multiple sclerosis and others.^[9]

FCGR2B may be a target for monoclonal antibody therapy for autoimmune diseases as well as malignancies.^[9][16][17]

See also

• CD32

References

Further reading

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.