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CD95 (Fas)-Based, Superantigen-Dependent, CD4⁺ T Cell-Mediated Down-Regulation of Human In Vitro Immunoglobulin Responses¹

William Stohl^2,*, Julie E. Elliott^*, David H. Lynch and Peter A. Kiener

^* Department of Medicine, Division of Rheumatology and Immunology, University of Southern California, Los Angeles, CA 90033; Department of Immunobiology, Immunex Corp., Seattle, WA 98101; and Department of Immunology and Inflammation, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543

Naturally occurring microbial superantigens (SAg) have been implicated in several human idiopathic disorders, and a compelling argument for the role of SAg in autoantibody-associated disorders, such as systemic lupus erythematosus, has been proposed. To test the effects of SAg on human in vitro Ig responses, CD4⁺ T cell + B cell cultures were stimulated with graded doses of staphylococcal enterotoxin B (SEB). Ig-secreting cell (IgSC) responses were very weak in CD4⁺ T cell + B cell cultures stimulated with SEB at the optimal mitogenic concentration (high dose SEB; 100 ng/ml) but were strong in parallel cultures stimulated with low dose SEB (0.01 ng/ml). High dose SEB actually enhanced B cell differentiation in the presence of CD4⁺ T cell soluble helper factors as long as the B cells were prevented from physically contacting the CD4⁺ T cells. However, when cell-cell contact between CD4⁺ T cells and B cells was permitted, high dose, but not low dose, SEB promoted increased CD4⁺ T cell-mediated B cell apoptosis with resulting decreases in viable CD20⁺ B cells and IgSC. High dose, but not low dose, SEB triggered increased levels of soluble CD95 ligand, and down-regulation of IgSC responses and incremental apoptosis of activated B cells were prevented by antagonist anti-CD95 mAb. This strongly suggests that CD4⁺ T cell-mediated CD95-based killing of activated B cells plays a major role in controlling SEB-driven IgSC responses. Defects in SAg-based down-regulation may contribute to autoimmune disorders such as SLE.

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				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]