STAPHYLOCOCCAL-ENTEROTOXIN-A INDUCES SURVIVAL OF V(H)3-EXPRESSING HUMAN B-CELL BY BINDING TO THE V-H REGION WITH LOW-AFFINITY

Staphylococcal enterotoxins (SE) are bacterial superantigens that bind to MHC class LI molecules and to the V beta-chain of the TCR, and sub sequently activate T cells expressing specific V beta regions. In this study, me have studied the effects of SEA on human B cell activation, and specifically the capacity of SEA to function as a B cell superant igen in vitro. We show herein that SEA failed to induce B cell prolife ration and differentiation in the absence of T cells. However, SEA ind uced survival of B cells uniquely expressing V(H)3 containing IgM, ind ependently of light chain utilization. The sequences of V(H)3 IgM gene products were determined and found to include a number of members of the V(H)3 family with a variety of different D and J(H) gene segments. Analysis of the sequences of V(H)3 gene products revealed possible si tes in framework region 1 and/or framework region 3 that could be invo lved in SEA-mediated activation of V(H)3-expressing B cells. Binding s tudies showed that SEA interacts with the V(H)3 domain of Ig with low, but detectable affinity. These results indicate that SEA functions as a B cell superantigen by interacting with V(H)3 gene segments of Ig.