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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1448-1455. Prepublished online as a Blood First Edition Paper on November 15, 2007; DOI 10.1182/blood-2007-10-117655. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-10-117655v1 111/3/1448    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 Rastelli, J. Articles by Zimber-Strobl, U. Search for Related Content PubMed PubMed Citation Articles by Rastelli, J. Articles by Zimber-Strobl, U. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 15, 2007 Accepted November 5, 2007 LMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class switch recombination to IgG1 Julia Rastelli, Cornelia Homig-Holzel, Jane Seagal, Werner Muller, Andrea C. Hermann, Klaus Rajewsky, and Ursula Zimber-Strobl* Institute of Clinical Molecular Biology and Tumor Genetics, GSF-National Research Center for Environment and Health, Munich, Germany CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA, United States Department of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute of Stem Cell Research, GSF-National Research Center for Environment and Health, Neuherberg, Germany * Corresponding author; email: strobl{at}gsf.de. The Epstein-Barr virus (EBV) protein LMP1 is considered to be a functional homologue of the CD40 receptor. However, in contrast to the latter, LMP1 is a constitutively active signaling molecule. To compare B cell specific LMP1 and CD40 signaling in an unambiguous manner, we generated transgenic mice conditionally expressing a CD40/LMP1 fusion protein, which retained the LMP1 cytoplasmic tail, but has lost the constitutive activity of LMP1 and needs to be activated by the CD40 ligand. We show that LMP1 signaling can completely substitute CD40 signaling in B cells, leading to normal B cell development, activation, and immune responses including class switch recombination, germinal center formation and somatic hypermutation. In addition, the LMP1-signaling domain has a unique property in that it can induce class switch recombination to IgG1 independent of cytokines. Thus, our data indicate that LMP1 has evolved to imitate T helper cell function allowing activation, proliferation and differentiation of EBV-infected B cells independent of T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. J. Kraus, H. Nakano, and G. A. Bishop TRAF5 is a critical mediator of in vitro signals and in vivo functions of LMP1, the viral oncogenic mimic of CD40 PNAS, October 6, 2009; 106(40): 17140 - 17145. [Abstract] [Full Text] [PDF] H. Kohlhof, F. Hampel, R. Hoffmann, H. Burtscher, U. H. Weidle, M. Holzel, D. Eick, U. Zimber-Strobl, and L. J. Strobl Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells Blood, May 28, 2009; 113(22): 5506 - 5515. [Abstract] [Full Text] [PDF] L. T. Krug, C. M. Collins, L. M. Gargano, and S. H. Speck NF-{kappa}B p50 Plays Distinct Roles in the Establishment and Control of Murine Gammaherpesvirus 68 Latency J. Virol., May 15, 2009; 83(10): 4732 - 4748. [Abstract] [Full Text] [PDF]

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