Fc gamma receptor III on human neutrophils. Allelic variants have functionally distinct capacities.

Abstract

As a model system to explore the functional consequences of structural variants of human Fcy receptors (FcyR), we have investigated Fc-yR-mediated phagocytosis in relation to the NA1-NA2 polymorphism of FcyRIII (CD16) on neutrophils (Fc'yRIIIpMN). The neutrophil-specific NA antigen system is a biallelic polymorphism with codominant expression demon- strating a gene dose effect with the anti-NAl MAb CLB-gran 11 in a large donor population. To explore the impact of this allelic variation of FcyRIIIPMN on phagocytosis, we used two FcyRIII-dependent probes, IgG-sensitized erythrocytes (EA) and concanavalin A-treated erythrocytes (E-ConA). Compari- son of FcyR-mediated phagocytosis by PMN from NA1 sub- jects and from NA2 subjects showed lower levels of phagocytosis of both probes by the NA2 individuals. The difference was most pronounced with lightly opsonized EA: at the lowest level of sensitization the phagocytic index was 72% lower for NA2 donors, whereas at the highest level of sensitization it was 21% lower (P < 0.003). Blockade of FcyRII with MAb IV.3 Fab amplified by threefold the difference between NAI and NA2 donors.