Low-affinity immunoglobulin gamma Fc region receptor IIb (FCGR2B) (FCGR2B)

Low-affinity immunoglobulin gamma Fc region receptor IIb (FCGR2B), also known as CD32b, is the sole inhibitory member of the Fc gamma receptor family and plays a pivotal role in maintaining immune homeostasis [1, 2]. It is primarily expressed on B cells, basophils, and various myeloid cells, where it functions via an Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) in its cytoplasmic tail [1, 3]. Upon co-ligation with the B-cell receptor (BCR) by immune complexes, FCGR2B recruits the phosphatase SHIP-1 to suppress B-cell activation, proliferation, and antibody production [3]. In autoimmune conditions such as systemic lupus erythematosus, reduced expression or genetic variants of this receptor are linked to the loss of B-cell tolerance [2, 3]. In the context of oncology, FCGR2B is frequently overexpressed on B-cell malignancies and can mediate the internalization of therapeutic antibodies, such as rituximab, thereby contributing to drug resistance [4]. Current therapeutic strategies include the development of antagonistic antibodies like BI-1206 to enhance the efficacy of anti-CD20 treatments in lymphoma, as well as agonistic molecules like obexelimab to suppress pathogenic B-cell activity in autoimmune diseases [4, 5].

Other names

CD32bFc-gamma RII-bFCGR2IgG Fc receptor II-bCD32FcRII-b

Drugs targeting FCGR2B act either as agonists to co-ligate the receptor with the B-cell receptor (BCR) to inhibit B-cell activation in autoimmune diseases, or as antagonists to block the inhibitory signal and prevent the internalization of other therapeutic antibodies in oncology.