Functional capacity of Fc gamma receptor III (CD16) on human neutrophils.
Receptors for the Fc region of immunoglobulin G (IgG) are a structurally diverse group of molecules. Within the three Fc gamma R families (Fc gamma RI, Fc gamma RII and Fc gamma RIII), the presence of distinct genes and alternative splicing variants leads to a variety of receptor isoforms that are most strikingly different in the transmembrane and intracellular regions. An obvious example of structural variation in the transmembrane and cytoplasmic domains is observed in the Fc gamma RIII family. Fc gamma RIIIB, which is nearly identical to Fc gamma RIIIA in the extracellular domains, lacks both transmembrane and cytoplasmic protein domains and is anchored to the cell through a glycosyl phosphatidylinositol anchor. Analysis of Fc gamma RIII function presents a considerable challenge in understanding the role of different Fc gamma R receptors in polymorphonuclear neutrophil (PMN) function. While one hypothesis for the role of Fc gamma RIII in Fc gamma R-dependent PMN effector functions is that Fc gamma RIII serves as a binding molecule which focuses the IgG ligand for more efficient recognition and intracellular signaling by Fc gamma RII, recent observations from a number of laboratories suggest that Fc gamma RIII on PMN can transduce signals across the membrane independent of ligand-dependent engagement of Fc gamma RII. We will review these data and present recent data which suggest that the role of Fc gamma RIII extends beyond direct initiation of functions to a more complex role of synergistic receptor interactions. These findings will be reviewed in the context of the experimental approaches that have been used to examine the roles of Fc gamma RII and Fc gamma RIII on PMN function.
Edberg
J C
JC
Hospital for Special Surgery, Cornell University Medical College, New York, NY 10021.
Salmon
J E
JE
Kimberly
R P
RP
D000911:Antibodies, Monoclonal; D006801:Humans; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology*; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D017452:Receptors, IgG