Induction of CD4+ T-cell anergy and apoptosis by activated human B cells

• Published in: Blood 2008-12, Vol.112 (12), p.4555-4564
• Main Authors: Tretter, Theresa, Venigalla, Ram K.C., Eckstein, Volker, Saffrich, Rainer, Sertel, Serkan, Ho, Anthony D., Lorenz, Hanns-Martin
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Apoptosis - immunology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biological and medical sciences; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - physiology; Cell Division - drug effects; Cell Division - immunology; Cell Proliferation - drug effects; Cells, Cultured; Clonal Anergy - immunology; Clonal Anergy - physiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Interleukin-2 - pharmacology; Interleukin-2 Receptor alpha Subunit - metabolism; Lymphocyte Activation - physiology; Organs and cells involved in the immune response; Up-Regulation - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-02-140087

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.