Role of receptor aggregation in complement-dependent inhibition of lymphocytes by high concentrations of concanavalin A

Abstract

EVIDENCE from haemolytic systems suggests that complement activation by either the classical or alternative pathways requires a close approximation of critical molecules at the cell surface. At least two molecules of IgG antibody in close proximity are required for the first component of complement to be bound¹. Thus when increasing concentrations of IgG are added to erythrocytes in the presence of excess complement, haemolysis is minimal until a critical IgG concentration is reached. In the case of the alternative (properdin) pathway of complement activation, at least two molecules of C3b must be critically orientated together at the cell surface in order for properdin to bind and stabilise C3/C5 convertase². Thus erythrocytes have a simple mechanism of signal discrimination by which they can ‘count’ the number of molecules reacting with their surfaces. The cells only ‘respond’ by lysis when a critical number has been reached. I present data which relate this mechanism of signal discrimination by erythrocytes to the mechanism by which cultured lymphocytes discriminate between low and high concentrations of the mitogenic lectin concanavalin A (con A). This in turn may be related to the mechanism by which lymphocytes discriminate between low and high concentrations of specific antigen to produce either an immune response or immunological tolerance³.