The Journal of Immunology, Vol 155, Issue 4 1838-1850, Copyright © 1995 by American Association of Immunologists

ARTICLES

Differential human T cell-dependent B cell differentiation induced by staphylococcal superantigens (SAg). Regulatory role for SAg-dependent B cell cytolysis

W Stohl and JE Elliott
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.

Microbial superantigens (SAg), by virtue of their binding to TCR V beta elements and to class II MHC molecules on accessory cells, trigger T cell proliferation in a dose-dependent fashion. In contrast, SAg- induced T cell-dependent B cell differentiation occurs only at SAg concentrations that are orders of magnitude lower that those required for optimal mitogenesis (low-dose SAg). At optimal mitogenic doses (high-dose SAg), SAg-driven B cell differentiation does not ensue. In this report, we demonstrate that this dichotomy in SAg-driven B cell differentiation is due to the active inhibition of B cell differentiation by high-dose SAg. Such inhibition is not reversed by feeding cultures with fresh medium, with conditioned media, or with IL2 +/- IL4, and impaired B cell differentiation is observed in cultures containing purified T cells or CD4+ T cells + B cells, as well as in PBMC cultures. Although preincubation of either T cells or B cells with high-dose SAg impairs subsequent SAg-induced B cell differentiation, high-dose SAg is not toxic per se, since high-dose SAg does promote vigorous B cell differentiation in cultures of mitomycin C-treated T cells + B cells and does not inhibit T cell-independent B cell differentiation. No correlation exists between SAg-induced B cell surface expression of CTLA4 ligand and generation of Ig-secreting cells, but the dose of SAg does correlate with T cell-mediated SAg- dependent cytolysis of transformed B cell targets or autologous nontransformed activated B cell targets. B cell recovery from cultures stimulated with high-dose SAg is lower than that from cultures stimulated with low-dose SAg, whereas B cell apoptosis is greater in the former cultures than that in the latter cultures. T cells stimulated with high-dose SAg do not inhibit differentiation of activated B cells in the absence of physical contact between the T cells and the target B cells, supporting the notion of direct killing of activated B cells by T cells. The ability of low doses of SAg to promote B cell differentiation without generating biologically meaningful cytolytic activity and the ability of higher doses of SAg to modulate Ig production may have important pathogenetic and therapeutic ramifications for certain autoimmune disorders, such as systemic lupus erythematosus.

This article has been cited by other articles:

				S. G. Zheng, J. D. Gray, K. Ohtsuka, S. Yamagiwa, and D. A. Horwitz Generation Ex Vivo of TGF-{beta}-Producing Regulatory T Cells from CD4+CD25- Precursors J. Immunol., October 15, 2002; 169(8): 4183 - 4189. [Abstract] [Full Text] [PDF]

				W. Stohl, D. Xu, S. Zang, K. S. Kim, L. Li, J. A. Hanson, S. A. Stohlman, C. S. David, and C. O. Jacob In vivo staphylococcal superantigen-driven polyclonal Ig responses in mice: dependence upon CD4+ cells and human MHC class II Int. Immunol., October 1, 2001; 13(10): 1291 - 1300. [Abstract] [Full Text] [PDF]

				W Stohl, A S Hamilton, D M Deapen, T M Mack, and D A Horwitz Impaired cytotoxic T lymphocyte activity in systemic lupus erythematosus following in vitro polyclonal T cell stimulation: a contributory role for non-T cells Lupus, May 1, 1999; 8(4): 293 - 299. [Abstract] [PDF]

				W. Stohl, D. H. Lynch, G. C. Starling, and P. A. Kiener Superantigen-Driven, CD8+ T Cell-Mediated Down-Regulation: CD95 (Fas)-Dependent Down-Regulation of Human Ig Responses Despite CD95-Independent Killing of Activated B Cells J. Immunol., October 1, 1998; 161(7): 3292 - 3298. [Abstract] [Full Text] [PDF]

				W. Stohl, J. E. Elliott, D. H. Lynch, and P. A. Kiener CD95 (Fas)-Based, Superantigen-Dependent, CD4+ T Cell-Mediated Down-Regulation of Human In Vitro Immunoglobulin Responses J. Immunol., June 1, 1998; 160(11): 5231 - 5238. [Abstract] [Full Text] [PDF]

				W. A. Ferens, W. C. Davis, M. J. Hamilton, Y. H. Park, C. F. Deobald, L. Fox, and G. Bohach Activation of Bovine Lymphocyte Subpopulations by Staphylococcal Enterotoxin C Infect. Immun., February 1, 1998; 66(2): 573 - 580. [Abstract] [Full Text] [PDF]