STAPHYLOCOCCAL-ENTEROTOXIN-D FUNCTIONS AS A HUMAN B-CELL SUPERANTIGENBY RESCUING V(H)4-EXPRESSING B-CELLS FROM APOPTOSIS

Staphylococcal enterotoxins are potent superantigens, in that they act ivate T cells bearing specific V beta-chain gene segments. In this stu dy, we analyzed the capacity of staphylococcal enterotoxin D (SED) to function as a B cell superantigen. SED induced T cell-dependent polycl onal proliferation and differentiation of B cells. In the absence of T cells, SED induced survival of B cells uniquely expressing V(H)4 cont aining IgM. The mechanism of survival of V(H)4-expressing B cells appe ared to relate to the countering of apoptosis initiated by the engagem ent of HLA-DR by SED. Analysis of the V(H)4 gene products expressed by SED-stimulated B cells revealed the usage of six of the known functio nal V(H)4 genes with a variety of different CDR3 regions,employing dif ferent D-H and J(H) gene segments. Moreover, the sequence analysis ide ntified a possible site for SED binding of V(H)4 that includes the sol vent-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(H)4 -expressing B cells.