Low affinity immunoglobulin gamma Fc region receptor (FcγR (Low-affinity))

The low affinity immunoglobulin gamma Fc region receptors (FcγRs) are a group of cell surface glycoproteins, including the FcγRII (CD32) and FcγRIII (CD16) subfamilies, that play a central role in bridging the adaptive and innate immune systems [3, 9]. These receptors are widely expressed on leukocytes, such as natural killer (NK) cells, macrophages, neutrophils, and B cells, where they recognize and bind the Fc portion of IgG-coated pathogens or immune complexes [12, 16]. Activating members, particularly FcγRIIIA (CD16A), are the primary mediators of antibody-dependent cellular cytotoxicity (ADCC), which is essential for the efficacy of many therapeutic monoclonal antibodies in oncology [4, 17]. Conversely, the inhibitory receptor FcγRIIB (CD32B) serves as a critical regulatory checkpoint that dampens B-cell receptor signaling and inflammatory responses to maintain immune homeostasis and self-tolerance [11, 13]. Therapeutic strategies often involve engineering the Fc domains of antibodies to optimize their affinity for these low-affinity receptors or developing targeted antibodies to either block or stimulate specific receptor pathways [4, 15]. Furthermore, genetic polymorphisms in the genes encoding these receptors, such as the FCGR3A V158F variant, are significant clinical biomarkers used to predict patient response to antibody-based treatments [17, 18].

Other names

CD16CD32Fc-gamma receptor IIFc-gamma receptor IIIFCGR2FCGR3FcRIIFcRIIILow affinity IgG receptor

Drugs interact with these receptors primarily by utilizing the Fc region of monoclonal antibodies to engage activating receptors (e.g., CD16A or CD32A), thereby triggering effector cell functions such as antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis [4, 18]. Alternatively, specialized therapies target the inhibitory receptor CD32B (FCGR2B) to suppress pathological B-cell activation or to overcome resistance to antibody therapies by preventing the internalization of surface antigens [1, 11].