Activated B cells express CD28/B7-independent costimulatory activity.
Resting and activated B cells display distinct phenotypes and functional properties. Resting B cells are incompetent accessory cells whereas activated B cells are capable of triggering T cell activation. The up-regulation of expression of the B7 family of molecules has been considered to be the primary reason for this functional conversion of activated B cells. We report here that activation of B cells induces a novel costimulatory activity for induction of T cell proliferation, which is independent of the CD28/B7 costimulatory pathway. B cells activated by different stimuli expressed comparable levels of many of the known counter-receptors for costimulation and intercellular adhesion (B7-1, B7-2, HSA, ICAM-1), but differed markedly in their capacity to activate CD4+ T cells from CD28-deficient (-/-) mice. Activation of B cells via CD40, and to a lesser extent with LPS, induced potent B7/CD28-independent costimulatory activity that resulted in marked augmentation of IL-2-mediated proliferative responses of CD4+ T cells from CD28 -/- mice. The B7/CD28-independent costimulatory pathway was capable of triggering the activation of naive CD4+ T cells, as both sorted CD45RBhigh and isolated high density naive CD4+ T cells from CD28 -/- mice responded vigorously to the costimulation provided by CD40L-activated B cells.
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Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Shevach
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EM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D005260:Female; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007739:L Cells; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D018122:B7-1 Antigen; D018106:CD28 Antigens; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D007476:Ionophores; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate