Low affinity immunoglobulin gamma Fc receptor IIb (FcγRIIb)

Low affinity immunoglobulin gamma Fc receptor IIb (FcγRIIb), also known as CD32b, is the only inhibitory member of the Fc gamma receptor family. It is primarily expressed on B cells, where it serves as a critical negative regulator of B-cell receptor (BCR) signaling, and on other myeloid cells like macrophages and dendritic cells to modulate inflammatory responses. By binding to the Fc region of IgG antibodies within immune complexes, FcγRIIb recruits the phosphatase SHIP1 to the cell membrane, which subsequently inhibits downstream activating signals. In the context of disease, reduced expression or functional polymorphisms of FcγRIIb are strongly associated with autoimmune disorders such as systemic lupus erythematosus due to the loss of B-cell tolerance. Conversely, in oncology, FcγRIIb is often overexpressed on B-cell malignancies and can limit the effectiveness of monoclonal antibody therapies by promoting the internalization of the drug-target complex. Therapeutic strategies include using agonistic antibodies to treat autoimmunity and antagonistic antibodies to enhance the anti-tumor activity of rituximab and other CD20-targeting agents.

Other names

CD32bFCGR2BFc-gamma RII-bFc gamma receptor IIBLow affinity immunoglobulin gamma Fc receptor II-b

Drugs targeting FcγRIIb typically act as either agonists to suppress overactive B cells in autoimmune diseases or as antagonists/blocking antibodies to prevent the inhibitory signal in cancer cells, thereby enhancing the efficacy of other therapeutic antibodies. Some engineered antibodies also increase their affinity for FcγRIIb to prolong half-life or modulate immune effector functions.