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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3715-3721. Prepublished online as a Blood First Edition Paper on August 6, 2007; DOI 10.1182/blood-2007-05-090142. This Article Full Text (PDF) All Versions of this Article: blood-2007-05-090142v1 110/10/3715    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 Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 14, 2007 Accepted July 30, 2007 Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival Christoph Mancao and Wolfgang Hammerschmidt* Department of Gene Vectors, GSF-National Research Center for Environment and Health, Munich, Germany * Corresponding author; email: hammerschmidt{at}gsf.de. Many cells latently infected with Epstein-Barr virus (EBV), including certain virus-associated tumors, express latent membrane protein 2A (LMP2A) suggesting an important role for this protein in viral latency and oncogenesis. LMP2A mimics B-cell receptor signaling but can also act as a decoy receptor blocking B-cell receptor (BCR) activation. Studies of peripheral B cells have not resolved this apparent contradiction because LMP2A seems to be dispensable for EBV-induced transformation of these B cells in vitro. We show here that LMP2A is essential for growth transformation of germinal center B cells, which do not express the genuine BCR because of deleterious somatic hypermutations in their immunoglobulin genes. BCR-positive (BCR+) and -negative (BCR-) B cells are readily transformed with a recombinant EBV encoding a conditional, floxed LMP2A allele but the survival and continued proliferation of both BCR+ and BCR- B cells is strictly dependent on LMP2A. These findings indicate that LMP2A has potent, distinct anti-apoptotic and/or transforming characteristics and point to its role as an indispensable BCR mimic in certain B cells from which human B-cell tumors such as Hodgkin's lymphoma originate. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Viral mimic for B-cell survival Ralf Küppers Blood 2007 110: 3494-3495. [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] C. Shannon-Lowe, E. Adland, A. I. Bell, H.-J. Delecluse, A. B. Rickinson, and M. Rowe Features Distinguishing Epstein-Barr Virus Infections of Epithelial Cells and B Cells: Viral Genome Expression, Genome Maintenance, and Genome Amplification J. Virol., August 1, 2009; 83(15): 7749 - 7760. [Abstract] [Full Text] [PDF] A. Carbone, E. Cesarman, M. Spina, A. Gloghini, and T. F. Schulz HIV-associated lymphomas and gamma-herpesviruses Blood, February 5, 2009; 113(6): 1213 - 1224. [Abstract] [Full Text] [PDF] L. J. Anderson and R. Longnecker Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell identity in vivo Blood, January 1, 2009; 113(1): 108 - 116. [Abstract] [Full Text] [PDF] L. J. Anderson and R. Longnecker EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway J. Gen. Virol., July 1, 2008; 89(7): 1563 - 1568. [Abstract] [Full Text] [PDF]

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