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Blood, 1 December 2003, Vol. 102, No. 12, pp. 4084-4089. Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-02-0518. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-02-0518v1 102/12/4084    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Durali, D. Articles by Taoufik, Y. Search for Related Content PubMed PubMed Citation Articles by Durali, D. Articles by Taoufik, Y. Related Collections Signal Transduction Gene Expression Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment Deniz Durali, Marie-Ghislaine de Goër de Herve, Julien Giron-Michel, Bruno Azzarone, Jean-François Delfraissy, and Yassine Taoufik From INSERM E-109, Université Paris-XI, Bicêtre, INSERM U-542, Villejuif, France; and Department of Biology, University of Quebec at Montreal (UQAM), Montreal, QE, Canada. Two functionally distinct subsets of B cells that produce Th1- and Th2-like patterns of cytokines have recently been identified. Interleukin-12 (IL-12) is a critical immunoregulatory cytokine that promotes Th1 differentiation through activation of signal transducer and activator of transcription 4 (STAT4). IL-12 has been reported to induce interferon (IFN-) production in B cells, but the relevant signaling pathways are poorly documented. Here, in human primary B cells, we found a functional IL-12 receptor (IL-12R) that internalizes following IL-12 binding. IFN- and, to a lesser extent, IL-12 positively regulated the IL-12R2 subunit but had no effect on IL-12R1. On examining the effect of IL-12 on STAT4 and T-bet (2 key factors involved in IFN- promoter activation), we found that IL-12 induced the phosphorylation and nuclear translocation of STAT4. IL-12-dependent constitutive STAT4 activation was also observed in the Epstein-Barr virus (EBV)-transformed B-cell line RPMI 8866 that spontaneously produces IL-12. T-bet expression has been shown to be dependent on STAT1. IL-12 had no direct effect on STAT1 activation or T-bet expression in primary B cells. In contrast, IL-12-induced IFN- led to STAT1 activation, strong expression of T-bet, and IFN- expression. IL-12 therefore initiates a cascade of events in B cells, including STAT4 activation, IL-12R2 up-regulation, IFN- production, and T-bet up-regulation, potentially leading to Th1-like differentiation. (Blood. 2003;102:4084-4089) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Ogawa, M. Funaba, and M. Tsujimoto A dual role of activin A in regulating immunoglobulin production of B cells J. Leukoc. Biol., June 1, 2008; 83(6): 1451 - 1458. [Abstract] [Full Text] [PDF] R. K. S. Phoon, A. R. Kitching, D. Odobasic, L. K. Jones, T. J. Semple, and S. R. Holdsworth T-bet Deficiency Attenuates Renal Injury in Experimental Crescentic Glomerulonephritis J. Am. Soc. Nephrol., March 1, 2008; 19(3): 477 - 485. [Abstract] [Full Text] [PDF] C. Atayar, A. van den Berg, T. Blokzijl, M. Boot, R. D Gascoyne, L. Visser, and S. 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