Low-affinity Fc gamma receptor (FcγR)

Low-affinity Fc gamma receptors (FcγRs) are a group of cell surface glycoproteins that bind the Fc region of immunoglobulin G (IgG) with low to moderate affinity, typically requiring the formation of multivalent immune complexes for stable interaction (1, 2). This group includes FcγRII (CD32) and FcγRIII (CD16), which are expressed across various immune cells such as natural killer (NK) cells, macrophages, neutrophils, and B cells (3). These receptors act as a bridge between the humoral and cellular immune systems, triggering essential effector functions like antibody-dependent cellular cytotoxicity (ADCC), phagocytosis, and the release of inflammatory mediators (1, 4). While activating receptors (e.g., FcγRIIA, FcγRIIIA) promote immune responses, the inhibitory receptor FcγRIIB provides a critical negative feedback loop to maintain immune tolerance and prevent autoimmunity (2, 5). In clinical practice, these receptors are major targets for therapeutic monoclonal antibodies, where Fc-engineering is used to optimize binding to activating receptors for oncology or to engage inhibitory receptors for treating autoimmune diseases (6). Citations: (1) Nimmerjahn F, Ravetch JV. Nat Rev Immunol. 2008;8(1):34-47. (2) Smith KG, Clatworthy MR. Nat Rev Immunol. 2010;10(5):328-343. (3) UniProt (P12318, P31994, P08637). (4) StatPearls: Physiology, Fc Receptors. (5) PubMed: PMC3434383. (6) DrugBank: Margetuximab, Obinutuzumab.

Other names

CD16CD32Fc gamma receptor IIFc gamma receptor IIIFCGR2FCGR3Low-affinity immunoglobulin gamma Fc region receptor

Enhancement of antibody-dependent cellular cytotoxicity (ADCC) through increased affinity for FcγRIIIA, inhibition of B-cell receptor signaling via FcγRIIB ligation, and competitive inhibition of pathogenic immune complex binding.