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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4555-4564. Prepublished online as a Blood First Edition Paper on September 18, 2008; DOI 10.1182/blood-2008-02-140087. This Article Full Text (PDF) All Versions of this Article: blood-2008-02-140087v1 112/12/4555    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tretter, T. Articles by Lorenz, H.-M. Search for Related Content PubMed PubMed Citation Articles by Tretter, T. Articles by Lorenz, H.-M. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 19, 2008 Accepted August 26, 2008 Induction of CD4+T cell anergy and apoptosis by activated human B cells Theresa Tretter*, Ram K.C. Venigalla, Volker Eckstein, Rainer Saffrich, Serkan Sertel, Anthony D. Ho, and Hanns-Martin Lorenz Division of Rheumatology, Department of Medicine V, University of Heidelberg, Heidelberg, Germany Division of Hematology and Oncology, Department of Medicine V, University of Heidelberg, Heidelberg, Germany Department of Otolaryngology, Clinics for Head and Neck Surgery, University of Heidelberg, Heidelberg, Germany * Corresponding author; email: theresa.tretter{at}med.uni-heidelberg.de. B cells are well known mediators of humoral immunity and serve as costimulators in the generation of T cell mediated responses. In a number of mouse models though, it was observed that B cells can also downregulate 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 downregulation 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 towards costimulatory effects triggered by B cells. We conclude that activated CD25+B cells are able to costimulate or downregulate T cell responses, depending on activation status and environmental conditions which might also influence their pathophysiological impact. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Activated human B cells: stimulatory or tolerogenic antigen-presenting cells? Alexander Shimabukuro-Vornhagen, Eisei Kondo, Tanja Liebig, and Michael von Bergwelt-Baildon Blood 2009 114: 746-747. [Full Text] [PDF] Response: Stimulatory or tolerogenic role of CD40-activated B cells depends on the strength of the activation to T cells Wenwei Tu, Jian Zheng, Yinping Liu, and Yu-Lung Lau Blood 2009 114: 747-748. [Full Text] [PDF] This article has been cited by other articles: A. Shimabukuro-Vornhagen, E. Kondo, T. Liebig, and M. von Bergwelt-Baildon Activated human B cells: stimulatory or tolerogenic antigen-presenting cells? Blood, July 16, 2009; 114(3): 746 - 747. [Full Text] [PDF]

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