ON THE INTERACTION OF IGG SUBCLASSES WITH THE LOW AFFINITY FC-GAMMA-RIIA (CD32) ON HUMAN MONOCYTES, NEUTROPHILS, AND PLATELETS - ANALYSIS OF A FUNCTIONAL POLYMORPHISM TO HUMAN IGG2

An allotypic form of the low affinity IgG Fc receptor FcgammaRIIa (CD32), termed low responder (LR) because of its weak reactivity with mouse (m) IgG1, interacts efficiently with human (h) IgG2. FcgammaRIIa(LR) is the first known human FcR that binds this IgG subclass. In this study, we analyzed the role of FcgammaRIIa in binding of stable hIgG-subclass dimers, and in induction of T cell mitogenesis using chimeric anti-CD3 mAb. We demonstrate that the functional polymorphism to hIgG2 is expressed on the majority of FcgammaR-bearing peripheral blood cells: monocytes, neutrophils, and platelets. We were able to assess FcgammaRII-mediated IgG-binding without interference of other FcgammaR-classes, by blockade of FcgammaRI on monocytes, and by using neutrophils of an individual deficient for the FcgammaRIIIB gene. This study indicates as subclass specificity: hIgG3 > hIgG1,hIgG2 much greater than hIgG4 for FcgammaRIIa(LR) and hIgG3,hIgG1 much greater than hIgG2 > hIgG4 for FcgammaRIIa(HR). Comparing the serum hIgG levels of individuals homozygous for the two FcgammaRIIa allotypic forms, we observed significantly lower hIgG2 serum levels in individuals expressing the hIgG2-binding LR allotypic form. This observation may implicate that FcyRIIa regulates hIgG subclass production or turnover in man.