An Fc receptor is a protein located on the surface of various immune cells that plays a critical role in the immune system's protective functions. It is named for its ability to recognize and bind the Fc portion of homologous or heterologous immunoglobulin molecules, thereby mediating biological functions. Fc receptors engage with antibodies bound to infected cells or pathogens, activating phagocytic or cytotoxic cells to eliminate these targets via mechanisms involving ADCC or antibody-mediated phagocytosis. Some viruses exploit Fc receptors to facilitate infection via antibody-dependent enhancement. The importance of Fc receptors lies in their ability to bridge the specificity of the adaptive immune system with the potent effector functions of innate immune cells.
Fig.1 Schematic diagram of Fc receptor.1
Fig.2 FcγR family and its distribution in human effector leukocytes.2, 4
| Fc-gamma receptors (FcγR): play a pivotal role in inducing the phagocytosis of opsonized (marked) microbes | FcγRI (CD64) | Initiation of respiratory burst; Cellular activation; Stimulation of microbial killing; Induction of phagocytosis; |
| FcγRIIA (CD32) | Phagocytosis; Degranulation (eosinophils); | |
| FcγRIIB1 (CD32) | Cell activity inhibition; | |
| FcγRIIB2 (CD32) | Phagocytosis; Cell activity inhibition; | |
| FcγRIIIA (CD16a) | ADCC; Stimulation of cytokine secretion by macrophages; | |
| FcγRIIIB (CD16b) | Induction of microbial eradication; | |
| Fc-alpha receptors (FcαR) | FcαRI (CD89) | Phagocytosis; Stimulation of microbial elimination; |
| Fcα/μR (CD351) | Endocytosis; Stimulation of microbial elimination; | |
| Fc-epsilon receptors (FcεR) | FcεRI | Degranulation; Phagocytosis; |
| FcεRII (CD23) | Potential adhesive molecule; Transport of IgE across the epithelium of the human intestine; Positive reinforcement mechanism to amplify allergic sensitization (B cells); | |
| Neonatal Fc Receptor | FcRn | Facilitating IgG passage from mother to fetus via the placenta and to the infant through milk; Preserving IgG integrity against degradation; Mediating IgG transfer across endothelial or epithelial barriers. |
Some Fc receptors (FcαRI, FcγRIIA, and FcγRIIIA) modulate immune responses through interactions with monomeric or dimeric immunoglobulins and immune complexes, which target them based on their ITAM motifs. These interactions trigger various cellular signaling pathways, influencing functions such as the production of cytokines, degranulation, phagocytosis lipid mediators, and superoxides. The outcome of these processes depends on the specific cell type involved and the external signals induced by the ligand binding.
Fig.3 FcγRII signaling pathways.3, 4
Fc receptors are expressed on various immune cells, enabling these cells to recognize and eliminate microbial pathogens by binding to antibodies attached to their surfaces. These interactions occur at the Fc region of the antibodies, activating the cells possessing the Fc receptors. Phagocyte activation, particularly through Fcγ receptors, leads to ingestion and killing of IgG-coated pathogens via phagocytosis. Another critical function involving Fc receptors is ADCC, where FcγRIII on NK cells triggers the release of cytotoxic molecules to kill antibody-targeted cells. FcεRI, found on granulocytes, plays a role in allergic reactions and defense against parasitic infections, triggering the rapid release of mediators upon cross-linking with IgE molecules and their receptors.
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