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

The Low affinity immunoglobulin gamma Fc region 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, 2]. It is primarily expressed on B cells, where it serves as a critical checkpoint by providing negative feedback to the B-cell receptor (BCR) through its intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM) [2, 5]. Beyond B cells, it is found on myeloid cells like macrophages and dendritic cells, where it modulates phagocytosis and inflammatory cytokine release [1, 5]. In the context of autoimmune diseases, FcγRIIB dysfunction or low expression is linked to the loss of self-tolerance and overproduction of autoantibodies, making it a target for agonistic therapies like obexelimab [4, 6]. Conversely, in oncology, FcγRIIB is often overexpressed on B-cell malignancies or within the tumor microenvironment, where it can mediate resistance to therapeutic antibodies by promoting their internalization or inhibiting antibody-dependent cellular cytotoxicity (ADCC) [3, 7]. Consequently, antagonistic antibodies such as BI-1206 are being developed to block these inhibitory signals and enhance the efficacy of anti-cancer immunotherapies [3, 8].

Other names

CD32BFCGR2BCD32Fc-gamma RII-bReceptor for Fc fragment of IgG low affinity IIb

Agonism of the receptor to trigger ITIM-mediated inhibitory signaling, thereby suppressing B-cell and myeloid cell activation; Antagonism to block the inhibitory signal, preventing the internalization of therapeutic antibodies and enhancing effector cell functions like ADCC.