Staphylococcal enterotoxin D functions as a human B cell superantigen by rescuing V_H4-expressing B cells from apoptosis

Staphylococcal enterotoxins are potent superantigens, in that they activate T cells bearing specific Vβ-chain gene segments. In this study, we analyzed the capacity of staphylococcal enterotoxin D (SED) to function as a B cell superantigen. SED induced T cell-dependent polyclonal proliferation and differentiation of B cells. In the absence of T cells, SED induced survival of B cells uniquely expressing V_H4 containing IgM. The mechanism of survival of V_H4-expressing B cells appeared to relate to the countering of apoptosis initiated by the engagement of HLA-DR by SED. Analysis of the V_H4 gene products expressed by SED-stimulated B cells revealed the usage of six of the known functional V_H4 genes with a variety of different CDR3 regions, employing different D_H and J_H gene segments. Moreover, the sequence analysis identified a possible site for SED binding of V_H4 that includes the solvent-exposed surfaces of 3′ CDR2/FR3 and/or FR1. Thus, SED appears to function as a unique B cell superantigen by inducing survival of V_H4-expressing B cells.