Low affinity immunoglobulin gamma Fc receptor IIb (FcγRIIB) (FcγRIIB)

Low affinity immunoglobulin gamma Fc receptor IIb (FcγRIIB), also known as CD32B, is the only inhibitory member of the Fc gamma receptor family and is a key regulator of immune cell activation (UniProt P31994). It is widely expressed on B cells, myeloid cells, and mast cells, where it functions to dampen immune responses by recruiting the phosphatase SHIP-1 to its cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) upon binding to IgG immune complexes (Smith & Clatworthy, 2010, Nature Reviews Immunology). In autoimmune diseases like systemic lupus erythematosus (SLE), impaired FcγRIIB function leads to the loss of B-cell tolerance and excessive autoantibody production, making it a target for agonistic therapies like obexelimab that aim to restore inhibitory signaling (Zenas BioPharma). In oncology, FcγRIIB is often exploited by tumor cells to internalize therapeutic antibodies or provide inhibitory signals that limit antibody-dependent cellular cytotoxicity (ADCC). Consequently, blocking antibodies such as BI-1206 are being investigated to enhance the efficacy of rituximab and other monoclonal antibodies in B-cell malignancies (BioInvent). The receptor's polymorphism, specifically the I232T variant, is a well-known genetic risk factor for SLE due to its reduced inhibitory capacity (Nimmerjahn & Ravetch, 2008, Nature Reviews Immunology). Beyond its role in B cells, FcγRIIB also regulates the activation of mast cells and basophils, influencing allergic responses. Therapeutic strategies targeting this receptor must carefully balance the need for immune suppression in autoimmunity with the need for immune activation in cancer.

Other names

CD32BFCGR2BCD32Fc-gamma RII-bFcRII-bLow affinity immunoglobulin gamma Fc receptor II-bInhibitory Fc gamma receptor IIb

Agonism of the receptor recruits SHIP-1 to the ITIM domain to inhibit B-cell receptor signaling in autoimmunity, while antagonism blocks the inhibitory signal or prevents receptor-mediated internalization of other therapeutic antibodies to enhance ADCC in oncology (Smith & Clatworthy, 2010, Nature Reviews Immunology; BioInvent).