B-CELL SUPERANTIGENS - DEFINITION AND POTENTIAL IMPACT ON THE IMMUNE-RESPONSE

Superantigens have been extremely helpful tools in exploring fundament al questions in immunobiology including mechanisms of cell activation, tolerance, and autoimmunity. Until recently, attention has been focus ed exclusively on T-cell superantigens. However, new data suggest that there are superantigens that directly activate B cells. By definition , these agents (1) stimulate a high frequency of B cells, (2) target B cells that have restricted usage of VH or VL family genes, and (3) bi nd to immunoglobulins outside the sites that bind conventional antigen s. A candidate B-cell superantigen that has received considerable atte ntion in this laboratory is staphylococcal protein A. This agent is be st known to the immunologist because of its ability to bind to the Fc fragment of IgG. This binding has been localized to two alpha-helical structures on each of four or five homologous regions that comprise th e extracellular domain of protein A. However, it is now clear that pro tein A contains a second site that binds to determinants on the Fab re gions of certain immunoglobulins independently of their heavy-chain is otype. In man this so-called alternative site appears to bind only to immunoglobulins that utilize heavy-chain genes of the VH3 subfamily. I n the mouse this type of binding is restricted to immunoglobulins usin g heavy chains belonging to the S107 and J606 VH families. In this rev iew, we examine the growing list of microbial products that dominate B -cell superantigenic properties. Using staphylococcal protein A as a m odel for a B-cell superantigen, we consider the potential impact of th is novel class of antigens on the immune response. We focus on the abi lity of B-cell superantigens to influence the expression of the B-cell repertoire. In addition, we consider the hypothesis that the interact ion of a B-cell superantigen with its reactive serum immunoglobulins a ctivates the classical complement cascade and thus represents a powerf ul stimulant of tissue inflammation.