Monocyte receptors for the Fc portion of IgG studies with monomeric human IgG1: normal in vitro expression of Fc gamma receptors in HLA-B8/Drw3 subjects with defective Fc gamma-mediated in vivo clearance

Abstract

The Fc gamma receptors of reticuloendothelial cells are presumed to play an important role in the clearance of circulating particles opsonized with IgG. In order to quantify these receptors and assess their contribution to the clearance phenomenon in man, Scatchard analysis has been applied to 125I-IgG1 myeloma protein binding by a model mononuclear phagocyte, the peripheral blood monocyte. Close compliance to the criteria for linear Scatchard plots has been obtained. The kinetics of binding at 37 degrees C were consistent with a simple, reversible, bimolecular reaction. A saturable, single class of high-affinity binding sites was discerned with a Ka of 2.61 +/- 0.13 x 10(8) M-1 and a mean of 35,500 +/- 1700 receptors per monocyte. These receptors expressed approximately equal affinities for IgG subclasses 1 and 3, with progressively lower affinities for IgG subclasses 4 and 2, respectively. Parameters of IgG1 binding to monocytes of patients with dermatitis herpetiformis and normal individuals of HLA-B8/Drw3 haplotype were not significantly different from controls, despite the previous demonstration of retarded IgG-mediated clearance in one-half of such subjects. Receptor number and affinity failed to correlate with T 1/2 for sensitized erythrocyte clearance in vivo. Functional defects in in vivo clearance, even in the absence of circulating immune complexes, are not necessarily related to abnormal expression of Fc gamma receptors by phagocytes.