Low affinity immunoglobulin gamma Fc region receptor IV (FcγRIV)

Mouse FcγRIV, encoded by the Fcgr4 gene, is a potent activating Fc gamma receptor expressed predominantly on myeloid cells, including neutrophils, monocytes, and macrophages (UniProt, P0C0L3). It serves as a critical mediator of the immune response by binding with high affinity to IgG2a and IgG2b immune complexes, subsequently triggering effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (Nimmerjahn et al., 2005, Immunity). In various disease models, FcγRIV has been identified as a key driver of inflammatory tissue injury, particularly in autoimmune conditions like rheumatoid arthritis and nephrotoxic nephritis (Hirano et al., 2007, Journal of Immunology). Furthermore, it is the primary receptor responsible for the therapeutic efficacy of many anti-tumor antibodies in mice, making it a focal point for preclinical oncology research (Nimmerjahn & Ravetch, 2008, Nature Reviews Immunology). Although it lacks a direct human ortholog, its functional profile most closely resembles human FcγRIIIa (CD16A), which is vital for translating mouse data to human clinical applications. Targeting or blocking FcγRIV with specific antibodies, such as the 9E9 clone, allows researchers to dissect the specific contributions of this receptor to pathology and therapeutic outcomes.

Other names

Fcgr4CD16-2Fc gamma RIV4833442P21Rik

FcγRIV acts by binding the Fc portion of IgG2a or IgG2b antibodies, which promotes the association with the ITAM-containing common gamma chain (FcRγ), leading to phosphorylation by Src-family kinases and subsequent activation of downstream signaling pathways like Syk and PLCγ (Nimmerjahn & Ravetch, 2005, Immunity).