Low affinity immunoglobulin gamma Fc region receptor II-a and II-b (FcγRIIa/FcγRIIb)

Fc gamma receptor IIa (FcγRIIa) and IIb (FcγRIIb), collectively referred to as CD32, are integral membrane glycoproteins that play a pivotal role in modulating the immune system's response to IgG-coated targets. FcγRIIa is an activating receptor characterized by an intracellular immunoreceptor tyrosine-based activation motif (ITAM), predominantly found on myeloid cells and platelets, where it triggers phagocytosis and pro-inflammatory cytokine release (UniProt P12318). Conversely, FcγRIIb is the sole inhibitory Fc gamma receptor, possessing an immunoreceptor tyrosine-based inhibition motif (ITIM) that serves to dampen B-cell receptor signaling and suppress myeloid cell activation (UniProt P31994). The functional equilibrium between these two receptors is essential for maintaining immune tolerance, and dysregulation is a hallmark of autoimmune conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (PubMed: 20847268). In oncology, therapeutic antibodies are often engineered to increase affinity for FcγRIIa to enhance antibody-dependent cellular cytotoxicity (ADCC), while in autoimmunity, drugs like obexelimab target FcγRIIb to inhibit autoreactive B cells (DrugBank: DB15034). Additionally, the presence of FcγRIIa on platelets means that targeting this receptor group requires careful management to avoid unintended platelet activation or clearance (PubMed: 25293375). Genetic polymorphisms in these receptors, such as the FCGR2A-H131R variant, significantly influence individual responses to monoclonal antibody therapies and susceptibility to infectious diseases (PubMed: 10438930).

Other names

CD32aCD32bFCGR2AFCGR2BFc-gamma RIIaFc-gamma RIIbCD32

Modulation of the activating (FcγRIIa) and inhibitory (FcγRIIb) signaling balance to either enhance immune effector functions or suppress pathological immune responses.