Neutrophil Fc-gamma receptors: a two-way bridge in the immune system

IS OF MAJOR importance in the humoral immune I system and is present in high concentrations in human plasma (10 mg/mL).The neutrophil is the most abundant cell in the cellular immune system (body content, =5 x 10" neutrophils).This review will focus on the receptors that mediate contact between IgG and human neutrophils: the neutrophil Fc-y receptors.The human neutrophil can express three distinct classes of Fc-y receptors: FcRI, FcRII, and FcRIII (reviewed in reference 1).During the last few years, remarkable data have been generated on the structure of these receptors; eg, the fact that one base substitution determines the linkage of FcRIII in the membrane.Moreover, soluble FcRs have been identified, revealing a more complicated immunoregulatory function of FcRs than the straightforward induction of clearance of antibody-coated blood cells or pathogens. STRUCTURE OF FcRsAll three FcRs are members of the immunoglobulin supergene family.FcRI is a 72-Kd protein.Its cDNA encodes for an extracellular region of about 290 amino acids, in which three immunoglobulin (1g)-like domains can be distinguished, as well as a 21 amino acid transmembrane region and a charged cytoplasmic domain.*FcRI is heavily glycosylated.After removal of the N-linked carbohydrates of FcRI (isolated from a monocytic cell line), a core protein of 55 Kd is found.3Blot hybridization of genomic DNA revealed a pattern consistent with at most two closely linked genes.The products of these genes differ in their cytoplasmic domain (61 versus 31 amino acids; J.V. Ravetch, personal communication, August 1989).FcRII precipitates as a sharp band of 40 Kd and after removal of the carbohydrates, as a band of 36 Kd.4 Its cDNA codes for an extracellular region of about 180 amino acids, containing two Ig-like domains: a 24 to 26 amino acid transmembrane region and a cytoplasmic domain of variable length (76, 52, and 44 amino acids; reference 5 and J.V. Ravetch, personal communication, August 1989).Three different genes (IIa, IIa', and IIb) have been identified for FcRII.The principal differences between IIa and IIb are a different signal peptide and a different cytoplasmic domain (76 amino acids for IIa and 40 to 50 amino acids for IIb).6,7The IIa' form contains a signal peptide similar to the IIb form and the cytoplasmic domain of the IIa form.Moreover, the IIb mRNA is alternatively spliced for the generation of -Way Bridge in the Immune Systemand Albert E.G.Kr.von dem Borne