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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4339-4344. Prepublished online as a Blood First Edition Paper on August 2, 2005; DOI 10.1182/blood-2005-06-2341. This Article Full Text (PDF) All Versions of this Article: 2005-06-2341v1 106/13/4339    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 Mancao, C. Articles by Hammerschmidt, W. Search for Related Content PubMed PubMed Citation Articles by Mancao, C. Articles by Hammerschmidt, W. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 13, 2005 Accepted July 27, 2005 Rescue of 'crippled' germinal center B cells from apoptosis by Epstein-Barr virus Christoph Mancao, Markus Altmann, Berit Jungnickel, and Wolfgang Hammerschmidt* Department of Gene Vectors, GSF - National Research Center for Environment and Health, Munich, Germany Institute for Clinical Molecular Biology and Tumor Genetics, GSF - National Research Center for Environment and Health, Munich, Germany * Corresponding author; email: hammerschmidt{at}gsf.de. Epstein-Barr virus (EBV) is associated with B cell lymphomas such as Hodgkin lymphoma, Burkitt lymphoma, and post-transplant lymphoma, which originate from clonal germinal center (GC) B cells. During the process of somatic hypermutation, GC B cells can acquire deleterious or nonsense mutations in the heavy and light immunoglobulin genes. Such mutations abrogate the cell surface expression of the B cell receptor (BCR), which results in the elimination of these non-functional B cells by immediate apoptosis. EBV encodes several latent genes, among them latent membrane protein 1 (LMP1) and LMP2A, which are regularly expressed in EBV-positive Hodgkin lymphoma and post-transplant lymphomas. Since LMP1 and LMP2A mimic the function of two key receptors on B cells, CD40 and BCR, respectively, we wanted to learn whether EBV infection can rescue pro-apoptotic GC B cells with crippling mutations in the heavy chain immunoglobulin locus from apoptosis. We show here that BCR-negative GC B cells readily enter the cell cycle upon infection with EBV in vitro and yield clonal lymphoblastoid cell lines that are incapable of expressing a functional BCR because the rearranged and formerly functional heavy chain immunoglobulin alleles carry deleterious mutations. Our findings imply an important role for EBV in the process of lymphomagenesis in certain cases of Hodgkin lymphoma and post-transplant lymphomas. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: EBV meets BCR- B cells Daniel Re Blood 2005 106: 4020-4021. [Full Text] [PDF] Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas Dörte Bechtel, Julia Kurth, Claus Unkel, and Ralf Küppers Blood 2005 106: 4345-4350. [Abstract] [Full Text] [PDF] This article has been cited by other articles: K. T. Bieging, A. C. Amick, and R. Longnecker Epstein-Barr virus LMP2A bypasses p53 inactivation in a MYC model of lymphomagenesis PNAS, October 20, 2009; 106(42): 17945 - 17950. [Abstract] [Full Text] [PDF] R. M'kacher, L. Andreoletti, S. Flamant, F. Milliat, T. Girinsky, J. Dossou, D. Violot, E. Assaf, B. Clausse, S. 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