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International Immunology, Vol. 13, No. 10, 1291-1300, October 2001
© 2001 Japanese Society for Immunology

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

William Stohl, Dong Xu, Song Zang,1, Kyung S. Kim, Lily Li,1, Julie A. Hanson,3, Stephen A. Stohlman,2, Chella S. David,3 and Chaim O. Jacob,1

Division of Rheumatology and Immunology,
1 Division of Gastrointestinal and Liver Diseases in the Department of Medicine, and
2 Department of Neurology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 711, Los Angeles, CA 90033, USA
3 Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA

Correspondence to: Correspondence to: W. Stohl

Staphylococcal enterotoxin (SE) B and seven other staphylococcal superantigens (SAg), despite promoting vigorous Ig production in human peripheral blood mononuclear cell cultures, are exceedingly poor at eliciting Ig responses in cultures of spleen cells from C57BL/10J (B10) or C3H/HeJ mice. In contrast, SEB elicits Ig responses in cultures of spleen cells from human MHC class II-transgenic mice. Whereas i.p. administration of SEB (0.2–20 µg) to non-transgenic B10 mice elicits very weak in vivo Ig responses, identical treatment of CD4+ cell-intact (but not CD4+ cell-depleted) human MHC class II-transgenic mice elicits dramatic increases in both splenic Ig-secreting 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 preferential increase in splenic CD8+ cells. Nevertheless, in vivo depletion of CD8+ cells has no sustained effect on SEB-driven Ig responses. Taken together, these observations demonstrate that the effects of SAg on in vivo humoral immune responses are highly CD4+ cell dependent, are substantially CD8+ cell independent and can be successfully investigated using human MHC class II-transgenic mice. This model system may be useful in investigating the polyclonally activating effects of microbial products (prototypic environmental insults) on the development of systemic autoimmunity.

Keywords: CD8+ cells, staphylococcal enterotoxin B, transgenic/knockout mice

Transmitting editor: T. Tedder


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