FCGR3Bs

FCGR3B, also known as Fc gamma receptor IIIb, is a gene that encodes a low-affinity receptor for the Fc region of IgG. The encoded protein is a glycoprotein receptor expressed primarily on neutrophils, where it is GPI-anchored to the cell surface and participates in the recognition and phagocytosis of IgG-coated particles and immune complexes.

Location and structure: FCGR3B is part of the FCGR gene cluster on chromosome 1, a cluster that also includes other Fc gamma receptor genes such as FCGR2A, FCGR2B, and FCGR3A. The receptor is a membrane protein anchored by a glycosylphosphatidylinositol (GPI) linkage, lacking a transmembrane or intracellular signaling domain. It binds IgG with relatively low affinity, with highest interaction toward IgG1 and IgG3 subclasses, facilitating opsonization and clearance of opsonized targets by neutrophils.

Genetic variation: The FCGR3B gene shows common allelic polymorphism and copy number variation (CNV). Allelic variants, including NA1 and NA2 haplotypes, can influence receptor binding and neutrophil function. In addition, CNV at the FCGR3B locus, ranging from deletions to duplications, alters receptor density on neutrophils and has been studied in relation to disease risk.

Clinical relevance: Variation in FCGR3B has been associated with susceptibility to autoimmune and inflammatory diseases, notably systemic lupus erythematosus (SLE). Lower copy number or receptor function can impair immune complex clearance by neutrophils, potentially contributing to disease pathogenesis. FCGR3B function also plays a role in neutrophil activation and inflammatory responses.

In summary, FCGR3B encodes a neutrophil-expressed, GPI-anchored IgG receptor that mediates immune complex clearance and influences susceptibility to certain autoimmune conditions through genetic and allelic diversity.