Low affinity immunoglobulin gamma Fc receptor IIb (CD32B) (CD32B)

Low affinity immunoglobulin gamma Fc receptor IIb (CD32B) is a single-pass type I transmembrane glycoprotein and the only inhibitory member of the Fc gamma receptor family (UniProt: P31994). It is primarily expressed on B cells, macrophages, dendritic cells, and neutrophils, where it plays a critical role in modulating immune responses by counteracting the signals from activating receptors (PubMed: 25324454). CD32B contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain, which, upon co-ligation with the B-cell receptor (BCR) or activating Fc receptors, recruits phosphatases like SHIP-1 to dampen cellular activation (NCBI Gene: 2213). In oncology, CD32B is often overexpressed in B-cell malignancies and can contribute to drug resistance by internalizing therapeutic antibodies like rituximab, thereby removing them from the cell surface (PubMed: 21045170). Conversely, in autoimmune diseases such as systemic lupus erythematosus, impaired CD32B function is linked to the loss of self-tolerance and overactive B-cell signaling (PubMed: 15153530). Therapeutic strategies targeting CD32B include monoclonal antibodies like BI-1206 designed to block its inhibitory function to enhance the efficacy of other immunotherapies, or agonists like obexelimab to suppress overactive immune cells in inflammatory conditions (ClinicalTrials.gov: NCT03571568).

Other names

FCGR2BCD32Fc-gamma RIIbFcRIIBCD32B antigenIGFR2

CD32B-targeted therapies function either as antagonists to prevent the internalization of other therapeutic antibodies and enhance ADCC, or as agonists to trigger the receptor's natural inhibitory signaling to suppress B-cell activity in autoimmune disorders (PubMed: 25324454, 21045170).