Selective activation of VH3A10+ rheumatoid factor producing B cells by staphylococcal enterotoxin D

Staphylococcal enterotoxin D (SED) is a T cell superantigenwhich selectively targets ß TCRs bearing particularV^ß elements. A second function of SED relates to thepreferential activation of a B cell subset characterized bya high frequency of rheumatoid factor (RF) producing B cells.To define the molecular basis of the SED-induced B cell repertoireshift, we have analyzed Ig heavy chain genes in B cell clonesexpanded after SED stimulation and compared them with B cellclones established in the presence of anti-CD3 stimulated helpercells. Gene segments of the V_H3 family were most frequentlyutilized under both stimulation conditions (42% anti-CD3; 47%SED). Sequence analysis of V_H3 gene segments demonstrated thatthe repertoire of V_H3 elements in B cell clones from SED drivenand anti-CD3 driven cultures were distinct (P=0.01). RF activitywas closely associated with the expression of selected V_H3 elements.B cell clones stimulated with SED preferentially expressed V_H3A10,whereas V_H26 was the gene segment dominantly used in B cellclones expanded with anti-CD3 stimulated helper cells. The usageof J_H and D_H elements was indistinguishable in SED and anti-CD3driven B cell clones, suggesting that SED targets V_H3⁺ B cellsthrough a V_H-specific mechanism. Comparison of the closely relatedsequences of the SED responsive V_H3A10 and the SED non-responsiveV_H26 element suggested a role of a sequence polymorphism inthe CDR2 reminiscent of B cell reactivity to conventional antigens.In contrast to conventional antigens, SED can induce differentiationof a high frequency of naive B cells. Thus, this staphylococcalenterotoxin combines selective activation of T cells with selectiveactivation of B cells and might be able to direct T cell helpto RF producing B cells.