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Staphylococcal Enterotoxin A Induces Survival of V_H3-Expressing Human B Cells by Binding to the V_H Region with Low Affinity¹

Department of Internal Medicine, Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75235

Staphylococcal enterotoxins (SE) are bacterial superantigens that bind to MHC class II molecules and to the Vß-chain of the TCR, and subsequently activate T cells expressing specific Vß 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 V_H3-containing IgM, independently of light chain utilization. The sequences of V_H3 IgM gene products were determined and found to include a number of members of the V_H3 family with a variety of different D and J_H gene segments. Analysis of the sequences of V_H3 gene products revealed possible sites in framework region 1 and/or framework region 3 that could be involved in SEA-mediated activation of V_H3-expressing B cells. Binding studies showed that SEA interacts with the V_H3 domain of Ig with low, but detectable affinity. These results indicate that SEA functions as a B cell superantigen by interacting with V_H3 gene segments of Ig.

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