Fc region of Immunoglobulin G (IgG) (IgG Fc)

The Fc (fragment crystallizable) region is the tail portion of an antibody that interacts with cell surface receptors known as Fc receptors and various proteins of the complement system. In IgG-class antibodies, the Fc region is composed of two identical protein fragments derived from the CH2 and CH3 constant domains of the heavy chains. This region is essential for the immune system's effector functions, including antibody-dependent cellular cytotoxicity (ADCC) and complement activation, which allow antibodies to bridge adaptive and innate immunity (3, 4). Beyond effector functions, the Fc region plays a critical role in antibody homeostasis by binding to the neonatal Fc receptor (FcRn). This interaction protects IgG from intracellular degradation, extending its serum half-life to approximately three weeks. In the context of autoimmune diseases, the Fc region of pathogenic autoantibodies is the functional target of FcRn-blocking therapies. By disrupting the Fc-FcRn interaction, these therapies accelerate the clearance of harmful antibodies, providing a targeted approach to reducing disease-driving immunoglobulin levels without broad immunosuppression (5, 6).

Other names

Fragment crystallizable regionIgG Fc domainFc fragmentImmunoglobulin G constant region

Drugs targeting the Fc-mediated pathway typically act as neonatal Fc receptor (FcRn) antagonists. By binding to FcRn with high affinity, these agents competitively inhibit the binding of endogenous IgG Fc regions to FcRn. This prevents the recycling of IgG antibodies back into the circulation, leading to their rapid lysosomal degradation and a subsequent reduction in the levels of pathogenic autoantibodies (1, 2).