Human T cell-dependent B cell differentiation induced by staphylococcal superantigens.
Microbial superantigens (SAgs), by virtue of their binding to TCR V beta elements on T cells and to class II MHC molecules on accessory cells (AC), trigger T cell activation. Although anti-CD3 mAb (which also trigger T cell activation via surface CD3/TCR) can readily induce T cell-dependent B cell differentiation in unmanipulated PBMC cultures, induction of Ig production in SAg-stimulated cultures has usually required special manipulation of the T cells, such as irradiating them or treating them with mitomycin C. We now demonstrate that eight different staphylococcal SAgs, typically at concentrations 10- to 100-fold lower than those required for proliferation, can each trigger unmanipulated peripheral blood and tonsil T cells to drive polyclonal B cell differentiation. Such SAg-induced T cell-dependent generation of Ig-secreting cells (IgSC) requires T cells and B cells only and occurs in the absence of monocytes as long as there are adequate numbers of B cells to serve as (DR+) AC. Physical contact among T cells, responder B cells, and AC (when different from the responder B cells) is required. The fusion protein CTLA4Ig inhibits SAg-induced IgSC generation in a dose-dependent fashion, whereas a control fusion protein has no such effect. In contrast, CTLA4Ig has, at best, only modest effects on SAg-induced T cell proliferation, indicating that CD28 (CTLA4)/B7 (B7-like) interactions play a more prominent role in SAg-induced IgSC generation than in SAg-induced T cell proliferation. These results establish SAg-induced T cell-dependent B cell differentiation as a useful model for T cell/B cell interactions, inasmuch as no other cell types are necessary for successful B cell differentiation; these results also demonstrate the importance of CD28 (CTLA4)/B7 (B7-like)-dependent mechanisms in this process.
Stohl
W
W
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Elliott
J E
JE
Linsley
P S
PS
D000069594:Abatacept; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018122:B7-1 Antigen / Q000502:physiology; D060908:CTLA-4 Antigen; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D018796:Immunoconjugates; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D013210:Staphylococcus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D018089:Superantigens; D000069594:Abatacept