Different functions for specific guinea pig IgG1 and IgG2 in the lysis of sheep erythrocytes by C4-deficient guinea pig serum.

Abstract

Abstract Binding of immune lgG1 and lgG2 to the sheep erythrocyte (E), a nonactivator of the alternative pathway, has been used to compare the roles of immunoglobulin subclasses in the activation of the alternative pathway in C4-deficient guinea pig serum. Radiolabeling of the subclasses permitted quantitative assessment of the specifically bound immunoglobulin. E sensitized with lgG1 (ElgG1) initiated activation of the alternative pathway as assessed by hemolysis and deposition of C3b, whereas E sensitized with lgG2 (ElgG2) did not. lgG2 in combination with lgG1 reduced the quantity of lgG1 required to achieve lysis, indicating a cooperative action of lgG2 in alternative pathway-dependent lysis once initiation had been mediated by the contribution of lgG1. F(ab’)2 fragments of lgG1 were active in initiating lysis, and both the Fab’ and F(ab’)2 fragments of lgG2 had a cooperative effect. Lysis was not affected when C4-deficient serum was chelated with Mg++EGTA, thereby ruling out the participation of the C1-bypass pathway. Desialated sheep E, capable of initiating alternative pathway-dependent lysis, underwent augmented lysis when bearing either lgG1 or lgG2, thus reflecting a cooperative action once the sheep E were altered to manifest an initiating function. The initiating function of the lgG1 subclass must relate to the formation of a site for the initial deposition of C3b, which is protected from β1H and C3b inactivator control; whereas the cooperative function of immunoglobulin bound to an activating surface must reflect an enhanced efficiency of the bound C3 and C5 convertases.