Studies on the mechanism of the complement-mediated inhibition of the Fc and C3 receptors of B lymphocytes

Abstract

The mechansim of the complement-mediated inhibition of the Fc receptors on human peripheral lymphocytes incubated with normal serum was studied. The pretreatment of lymphocytes with a purified C1-esterase inhibitor preparation almost completely blocked the inhibitory effect of the serum on the binding of FITC-conjugated IgG molecules. Twenty to twenty-five percent of the cells in a lymphocyte suspension incubated in normal human serum became immune adherance positive. When normal lymphocytes were treated with a C3 preparation, no inhibition of the IgG aggregate binding occurred. However, if the C3b fragments were cleaved from the C3 molecules in the presence of lymphocytes a strong inhibitory effect on the Fc receptors was observed. The same inhibition by C3b was demonstrated after the digestion of the C3b receptors from the surface of lymphocytes. Furthermore, the EAC rosette formation was inhibited on lymphocytes incubated in normal serum. Pretreatment of the cells by C1-esterase inhibitor or elimination of C1 by EDTA also strongly reduced this effect of the serum. It was concluded from these findings that C1 present on the surface of lymphocytes triggers the classical pathway activation in the serum. During the complement activation, C4b and C3b fragments are cleaved from the C4b and C3 molecules. Part of these fragments fixes to the C3b receptors of the B lymphocytes and inhibits the ability of these cells to form EAC rosettes. The second part of the C4 and C3b fragments binds to the membrane of lymphocytes through their labile binding site outside the C3b receptors. The possible relationship of the portion of lymphocyte membrane which fixes the labile binding sites of the complement-derived fragments and the Fc receptors is discussed.