Human Immunoglobulin G Fc region (IgG Fc) (IgG Fc)

The Human Immunoglobulin G (IgG) Fc region is the C-terminal portion of the IgG antibody molecule, consisting of the paired CH2 and CH3 constant domains of the heavy chains. It serves as the critical link between the adaptive immune system's specificity and innate effector mechanisms. By binding to various Fc gamma receptors (FcγRs) on leukocytes, the Fc region triggers processes such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and the release of inflammatory mediators (Nimmerjahn & Ravetch, 2008). It also initiates the classical complement pathway by binding to C1q, leading to complement-dependent cytotoxicity (CDC) (Diebolder et al., 2014). Beyond immune activation, the Fc region is the primary determinant of IgG longevity; its pH-dependent interaction with the neonatal Fc receptor (FcRn) within endothelial and myeloid cells rescues IgG from lysosomal degradation, extending its half-life to approximately 21 days (Roopenian & Akilesh, 2007). In autoimmune pathologies, the Fc region of autoantibodies mediates tissue destruction and allows for the persistence of these harmful proteins via FcRn recycling. Therapeutic targeting of the Fc region includes the use of the bacterial enzyme Imlifidase, which cleaves the IgG molecule at the hinge region to neutralize its effector functions, and the development of FcRn inhibitors that block the Fc-binding site on the receptor to accelerate the clearance of pathogenic IgG (Jordan et al., 2017; Gable & Guptill, 2020).

Other names

Fragment crystallizable regionFc fragmentIgG Fc domainCH2-CH3 domainConstant region of IgG

Proteolytic cleavage of the IgG heavy chain at the hinge region to physically separate the Fc region from the Fab fragments, thereby abolishing effector functions; Blockade of the neonatal Fc receptor (FcRn) to prevent the pH-dependent recycling of the Fc region and promote lysosomal degradation of IgG.