Binding of monomeric human IgG defines an expression polymorphism of Fc gamma RIII on large granular lymphocyte/natural killer cells.

Abstract

Human PBL express one or more of the three classes of Fc receptors for IgG (Fc gamma receptors, I, II, and III). Each type of Fc gamma receptor has a characteristic binding pattern for isotypes of human and mouse IgG. Large granular lymphocyte/NK cells (LGL/NK cells) express the transmembrane form of Fc gamma RIII (Fc gamma RIIIa) on their surface, whereas polymorphonuclear neutrophils (PMN) express the glycosyl phosphatidyl inositol-linked receptor that is the product of the Fc gamma RIIIB gene. Fc gamma RIII has been reported to have low affinity for monomeric IgG, regardless of the cell type on which it is expressed. This study demonstrates specific and saturable binding of monomeric human IgG (M-IgG) to Fc gamma RIIIa on LGL/NK cells but not to Fc gamma RIIIb on PMN. M-IgG binding revealed an expression polymorphism between individuals, those with either high (12,000 to 15,000) or low (4,000 to 7,000) binding sites per cell. Both high and low M-IgG-binding LGL/NK cells bound hulgG1 and IgG3 but did not bind IgG2 or IgG4. The high/low Fc gamma RIIIA expression polymorphism correlated with the ability of an individual's LGL/NK cells to perform antibody-dependent cellular cytotoxicity of erythroid cell targets.