Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B) (FCGR2B)

FCGR2B (CD32B) is the sole inhibitory member of the Fc gamma receptor (FcγR) family, playing a pivotal role in the negative regulation of immune responses (UniProt P31994; Wikipedia). It is widely expressed on B cells, monocytes, macrophages, and dendritic cells, where it functions as a molecular brake to prevent overactivation of the immune system (GeneCards; NIH). Upon binding to the Fc region of IgG immune complexes, FCGR2B recruits the phosphatase SHIP1 to its cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM), thereby antagonizing activating signals from the B-cell receptor (BCR) or other Fc receptors (Wikipedia; NIH). In oncology, FCGR2B is often overexpressed in B-cell malignancies, where it can mediate the internalization of therapeutic antibodies like rituximab, leading to drug resistance (NIH; BioInvent). Conversely, genetic variants or reduced expression of FCGR2B are strongly associated with autoimmune diseases such as systemic lupus erythematosus (SLE) due to the loss of B-cell tolerance (GeneCards; NIH). Therapeutic approaches targeting FCGR2B include antagonistic antibodies like BI-1206 to enhance the efficacy of anti-cancer treatments and agonistic or bifunctional molecules like obexelimab designed to suppress pathogenic B-cell activity in autoimmune conditions (BioInvent; Zenas BioPharma).

Other names

CD32CD32BFCG2FCGR2IGFR2FcRII-cFc-gamma RII-bFc fragment of IgG receptor IIb

Antagonism to block inhibitory signaling in cancer to enhance ADCC and prevent antibody internalization; Agonism or co-ligation with BCR to inhibit B-cell activation and autoantibody production in autoimmune diseases; Fc-engineering of antibodies to reduce binding to inhibitory FCGR2B while increasing binding to activating receptors.