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

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 f...

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Main Authors: Tretter, Theresa (Author) , Venigalla, Ram Kumar Chowdary (Author) , Eckstein, Volker (Author) , Saffrich, Rainer (Author) , Sertel, Serkan (Author) , Ho, Anthony Dick (Author) , Lorenz, Hanns-Martin (Author)
Format: Article (Journal)
Language:English
Published: [2008]
In: Blood
Year: 2008, Volume: 112, Issue: 12, Pages: 4555-4564
ISSN:1528-0020
DOI:10.1182/blood-2008-02-140087
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2008-02-140087
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006497120518041
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Author Notes:Theresa Tretter, Ram K.C. Venigalla, Volker Eckstein, Rainer Saffrich, Serkan Sertel, Anthony D. Ho, and Hanns-Martin Lorenz
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Summary: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.
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Physical Description:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2008-02-140087