In vivo staphylococcal superantigen-driven polyclonal Ig responses in mice: dependence upon CD4(+) cells and human MHC class II

Staphylococcal enterotoxin (SE) B and seven other staphylococcal superantig ens (SAg), despite promoting vigorous Ig production in human peripheral blo od mononuclear cell cultures, are exceedingly poor at eliciting Ig response s in cultures of spleen cells from C57BL/10J (B10) or C3H/HeJ mice. In cont rast, SEB elicits Ig responses in cultures of spleen cells from human MHC c lass II-transgenic mice. Whereas Lp. administration of SEB (0.2-20 mug) to non-transgenic B10 mice elicits very weak in vivo Ig responses, identical t reatment of CD4(+) cell-intact (but not CD4(+) cell-depleted) human MHC cla ss II-transgenic mice elicits dramatic increases in both splenic Ig-secreti ng cells and serum Ig levels. Over a 2-week period, the SEB-induced in vivo Ig responses peak and then plateau or fall in association with a preferent ial increase in splenic CD8(+) cells. Nevertheless, in vivo depletion of CD 8(+) cells has no sustained effect on SEB-driven Ig responses. Taken togeth er, these observations demonstrate that the effects of SAg on in vivo humor al immune responses are highly CD4(+) cell dependent, are substantially CD8 (+) cell independent and can be successfully investigated using human MHC c lass II-transgenic mice. This model system may be useful in investigating t he polyclonally activating effects of microbial products (prototypic enviro nmental insults) on the development of systemic autoimmunity.