FcRs

Fc receptors (FcRs) are cell-surface proteins that recognize the constant (Fc) region of antibodies. By binding antibody-coated targets, FcRs translate humoral recognition into cellular responses such as phagocytosis, cytokine release, antibody-dependent cellular cytotoxicity, and antigen presentation. They are expressed on a variety of immune and some non-immune cells, including macrophages, neutrophils, natural killer cells, dendritic cells, B cells, mast cells, basophils, and platelets.

The best-characterized families are Fc gamma receptors (FcγRs) for IgG, Fc alpha receptors (FcαRs) for IgA, Fc epsilon receptors (FcεRs) for IgE, and Fc mu receptors (FcμRs) for IgM. FcγRs include high-affinity FcγRI and lower-affinity FcγRII and FcγRIII members; among them, FcγRI mediates strong phagocytosis, while FcγRII and FcγRIII mediate activating or inhibitory signals depending on their intracellular motifs. FcγRIIB is inhibitory and helps limit immune activation. FcεRI is a high-affinity receptor on mast cells and basophils that drives allergic degranulation. FcαRI (CD89) engages IgA on myeloid cells, and FcμR binds IgM to modulate B cell signaling.

Signaling is typically through immunoreceptor tyrosine-based activation motifs (ITAMs) in associated gamma chains or DAP12 for activating receptors, whereas FcγRIIB contains an ITIM that dampens activation. Receptors often require clustering by immune complexes to elicit robust signaling.

Clinical relevance includes the dependence of many therapeutic antibodies on Fc–FcR interactions to induce effector functions such as ADCC and phagocytosis. Genetic polymorphisms and expression levels of FcRs can influence susceptibility to autoimmune diseases and responses to immunotherapies.