FcRII

FcRII, or Fc gamma receptor II, is a class of low-affinity receptors for the Fc region of immunoglobulin G (IgG). It comprises several isoforms encoded by the FCGR2 gene cluster (FCGR2A, FCGR2B, FCGR2C) and is expressed on a range of immune cells. FcRII receptors bind immune complexes and translate antibody recognition into cellular responses, helping regulate phagocytosis, cytokine production, antigen presentation, and, in some contexts, antibody-dependent cellular cytotoxicity.

The main subtypes are FcγRIIa (CD32a) and FcγRIIb (CD32b), with FcγRIIc (CD32c) present in a subset of individuals. FcγRIIa is an activating receptor expressed on neutrophils, monocytes, macrophages, and platelets. It signals via association with the common γ-chain, which contains ITAM motifs, and binds IgG1 and IgG3 with higher affinity, contributing to phagocytosis and respiratory burst. FcγRIIb is an inhibitory receptor found on B cells, dendritic cells, and some myeloid cells; it contains an ITIM in its cytoplasmic tail and dampens activation signals, notably B cell receptor signaling, to help limit immune responses and prevent autoimmunity. FcγRIIc is variably expressed due to genetic differences and is often considered nonfunctional in many individuals.

Clinical relevance of FcRII centers on the balance between activating and inhibitory signaling. Polymorphisms and gene copy-number variations can affect receptor expression and IgG subclass binding, influencing susceptibility to infections, autoimmune diseases, and responses to monoclonal antibody therapies. The FcγRII family thus plays a key role in immune complex handling, inflammation, and therapeutic outcomes.