Staphylococcal Enterotoxin A Induces Survival of VH3-Expressing Human B Cells by Binding to the VH Region with Low Affinity

Abstract

Staphylococcal enterotoxins (SE) are bacterial superantigens that bind to MHC class II molecules and to the Vβ-chain of the TCR, and subsequently activate T cells expressing specific Vβ regions. In this study, we have studied the effects of SEA on human B cell activation, and specifically the capacity of SEA to function as a B cell superantigen in vitro. We show herein that SEA failed to induce B cell proliferation and differentiation in the absence of T cells. However, SEA induced survival of B cells uniquely expressing VH3-containing IgM, independently of light chain utilization. The sequences of VH3 IgM gene products were determined and found to include a number of members of the VH3 family with a variety of different D and JH gene segments. Analysis of the sequences of VH3 gene products revealed possible sites in framework region 1 and/or framework region 3 that could be involved in SEA-mediated activation of VH3-expressing B cells. Binding studies showed that SEA interacts with the VH3 domain of Ig with low, but detectable affinity. These results indicate that SEA functions as a B cell superantigen by interacting with VH3 gene segments of Ig.