title: Induction of CD4+ T-cell anergy and apoptosis by activated human B cells.
abstract: B cells are well-known mediators of humoral immunity and serve as costimulators in the generation of T cell-mediated responses. In several mouse models, however, it was observed that B cells can also down-regulate immune reactions, suggesting a dual role for B cells. Due to this discrepancy and so far limited data, we directly tested the effects of primary human B cells on activated CD4(+) T helper cells in vitro. We found that under optimal costimulation large, activated CD25(+) B cells but not small CD25(-) B cells induced temporary T-cell anergy, determined by cell division arrest and down-regulation of cytokine production. In addition, large CD25(+) B cells directly induced CD95-independent apoptosis in a subpopulation of activated T cells. Suppression required direct B-T-cell contact and was not transferable from T to T cell, excluding potential involvement of regulatory T cells. Moreover, inhibitory effects involved an IL-2-dependent mechanism, since decreasing concentrations of IL-2 led to a shift from inhibitory toward costimulatory effects triggered by B cells. We conclude that activated CD25(+) B cells are able to costimulate or down-regulate T-cell responses, depending on activation status and environmental conditions that might also influence their pathophysiological impact.
authors.affiliation: Department of Medicine V, Divisions of Rheumatology, Clinics of Head and Neck Surgery, University of Heidelberg, Heidelberg, Germany. theresa.tretter@med.uni-heidelberg.de
authors.forename: Theresa
authors.initials: T
authors.lastname: Tretter
authors.forename: Ram K C
authors.initials: RK
authors.lastname: Venigalla
authors.forename: Volker
authors.initials: V
authors.lastname: Eckstein
authors.forename: Rainer
authors.initials: R
authors.lastname: Saffrich
authors.forename: Serkan
authors.initials: S
authors.lastname: Sertel
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Hanns-Martin
authors.initials: HM
authors.lastname: Lorenz
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit