Low affinity immunoglobulin gamma Fc receptor II-b (FcγRIIB)

Low affinity immunoglobulin gamma Fc receptor II-b (FcγRIIB), also known as CD32B, is a single-chain transmembrane glycoprotein and the only inhibitory member of the Fc gamma receptor family [1]. It is primarily expressed on B cells, myeloid cells, and mast cells, where it plays a critical role in maintaining immune homeostasis by terminating signal transduction through its cytoplasmic Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) [2]. In B cells, co-ligation of FcγRIIB with the B-cell receptor (BCR) by immune complexes leads to the recruitment of phosphatases like SHIP1, which inhibit B-cell activation, proliferation, and antibody production [3]. Dysregulation or genetic polymorphisms of FcγRIIB, such as the I232T variant, are strongly associated with autoimmune diseases like systemic lupus erythematosus (SLE) due to the loss of this inhibitory control [4]. In oncology, FcγRIIB is often overexpressed on B-cell malignancies and can mediate the internalization of therapeutic antibodies, such as Rituximab, thereby reducing their clinical efficacy [5]. Consequently, therapeutic strategies include agonistic antibodies to treat autoimmunity by suppressing B-cell activity and antagonistic antibodies to enhance the effectiveness of monoclonal antibodies in cancer treatment [6].

Other names

CD32BFCGR2BCD32Fc-gamma RII-bFc gamma receptor IIBLow affinity immunoglobulin gamma Fc receptor IIB

Agonism of FcγRIIB leads to the recruitment of SHIP1 phosphatase via its ITIM domain, which inhibits B-cell receptor (BCR) signaling and suppresses B-cell activation and plasma cell differentiation. Conversely, antagonism or blocking of FcγRIIB prevents the internalization of therapeutic monoclonal antibodies in cancer cells, thereby enhancing antibody-dependent cellular cytotoxicity (ADCC) and clinical efficacy.