Polyclonal in vitro T cell proliferation and T cell-dependent B cell differentiation supported by activated autologous B cells.
Although anti-CD3-induced T cell proliferation and T cell-dependent B cell differentiation are not supported well by resting (nonactivated) B cells as AC, human peripheral blood B cells activated in vitro with SAC, rIL2, or anti-IgM effectively subserve AC function in a manner qualitatively similar to that of blood monocytes and support polyclonal anti-CD3-driven T cell-dependent B cell differentiation. Physical contact among T cells, responder B cells, and (irradiated) activated B cells is required, and the ability of activated B cells to support anti-CD3-driven generation of IgSC parallels surface B7 expression by the activated B cells. The fusion protein CTLA4Ig, which binds to B7 and B7-like molecules with high avidity and disrupts the interaction of T cell surface CD28 with B7, inhibits B cell differentiation in a dose-dependent fashion, whereas a control fusion protein has no such effect. Thus, activated B cells support polyclonal T cell-dependent B cell differentiation via a CD28 (CTLA4)/B7 (B7-like)-dependent mechanism.
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; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology*; D018122:B7-1 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D060908:CTLA-4 Antigen; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007376:Interleukin-2; D000069594:Abatacept