Fragment crystallizable region of Immunoglobulin G (Fc region) (Fc region)

The Fragment crystallizable (Fc) region is the C-terminal portion of an antibody molecule, composed of the constant domains of the heavy chains. When an antibody binds to its specific antigen on a target cell, the Fc region becomes accessible to interact with Fc receptors (FcRs) on immune effector cells and proteins of the complement system (Vidarsson et al., 2014). This interaction is the primary mechanism by which the humoral immune response bridges to cellular effector functions, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC) (Wang et al., 2018). In therapeutic contexts, the Fc region is a target for engineering to enhance the potency of monoclonal antibodies or for pharmacological blockade to treat autoimmune diseases. For instance, neonatal Fc receptor (FcRn) inhibitors target the Fc-binding site to accelerate the clearance of pathogenic autoantibodies in conditions like myasthenia gravis (Gable & Guptill, 2022). Additionally, the Fc region's interaction with FcRn is exploited to extend the half-life of therapeutic proteins through Fc-fusion technology (Ulrichts et al., 2018).

Other names

Fc domainFc fragmentAntibody constant regionIgG Fc

The Fc region mediates its effects through three primary mechanisms: 1) Binding to Fc-gamma receptors (FcγRI, II, and III) on effector cells like NK cells and macrophages to induce antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP); 2) Binding to the C1q component of the complement system to trigger the classical complement pathway and complement-dependent cytotoxicity (CDC); and 3) Interaction with the neonatal Fc receptor (FcRn) to regulate the recycling and long serum half-life of IgG antibodies (Vidarsson et al., 2014; Wang et al., 2018).