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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1519-1529. Prepublished online as a Blood First Edition Paper on March 28, 2007; DOI 10.1182/blood-2006-10-053793. This Article Full Text (PDF) All Versions of this Article: blood-2006-10-053793v1 110/5/1519    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 Reichardt, P. Articles by Gunzer, M. Search for Related Content PubMed PubMed Citation Articles by Reichardt, P. Articles by Gunzer, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 23, 2006 Accepted March 22, 2007 Naive B-cells generate regulatory T-cells in the presence of a mature immunological synapse Peter Reichardt, Bastian Dornbach, Song Rong, Stefan Beissert, Faikah Gueler, Karin Loser, and Matthias Gunzer* Junior Research Group Immunodynamics, Helmholtz Centre for Infection Research, Braunschweig, Germany Department of Nephrology, Hannover Medical School, Hannover, Germany Department of Dermatology, and Interdisciplinary Center of Clinical Research, University of Munster, Munster, Germany * Corresponding author; email: mgunzer{at}helmholtz-hzi.de. Naive B-cells are ineffective antigen-presenting cells and considered unable to activate naive T-cells. However, antigen-specific contact of these cells leads to stable cell pairs that remain associated over hours in vivo. The physiological role of such pairs is not evaluated. We show here that antigen-specific conjugates between naive B-cells and naive T-cells display a mature immunological synapse in the contact zone which is absent in T-cell-dendritic cell (DC) pairs. B-cells induce substantial proliferation but contrary to DC no loss of L-Selectin in T-cells. Surprisingly, while DC-triggered T-cells develop into normal effector cells, B-cell stimulation over 72 hours induces regulatory T-cells inhibiting priming of fresh T-cells in a contactdependent manner in vitro. In vivo, the regulatory T-cells home to lymph nodes where they potently suppress immune responses such as in cutaneous hypersensitivity and ectopic allogeneic heart transplant rejection. Our finding might help to explain old observations on tolerance induction by B-cells, identifies the mature immunological synapse as a central functional module of this process, and suggests the use of naive B-cell-primed regulatory Tcells, "bTregs", as useful approach for therapeutic intervention in adverse adaptive immune responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. H. Hosseini, I. Louban, D. Djandji, G. H. Wabnitz, J. Deeg, N. Bulbuc, Y. Samstag, M. Gunzer, J. P. Spatz, and G. J. Hammerling Immune synapse formation determines interaction forces between T cells and antigen-presenting cells measured by atomic force microscopy PNAS, October 20, 2009; 106(42): 17852 - 17857. [Abstract] [Full Text] [PDF] A. Shimabukuro-Vornhagen, E. Kondo, T. Liebig, and M. von Bergwelt-Baildon Activated human B cells: stimulatory or tolerogenic antigen-presenting cells? 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CD20, CD3, and CD40 Ligand Microclusters Segregate Three-Dimensionally In Vivo at B-Cell-T-Cell Immunological Synapses after Viral Immunity in Primate Brain J. Virol., October 15, 2008; 82(20): 9978 - 9993. [Abstract] [Full Text] [PDF] F. Frommer, T. J. A. J. Heinen, F. T. Wunderlich, N. Yogev, T. Buch, A. Roers, E. Bettelli, W. Muller, S. M. Anderton, and A. Waisman Tolerance without Clonal Expansion: Self-Antigen-Expressing B Cells Program Self-Reactive T Cells for Future Deletion J. Immunol., October 15, 2008; 181(8): 5748 - 5759. [Abstract] [Full Text] [PDF] S. Balkow, F. Krux, K. Loser, J. U. Becker, S. Grabbe, and U. Dittmer Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naive T cells, and favors expansion of regulatory T cells Blood, December 1, 2007; 110(12): 3949 - 3958. [Abstract] [Full Text] [PDF]

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