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Open Access Green as soon as Postprint is submitted to ZB.
Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival.
Blood 110, 3715-3721 (2007)
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 BCR-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 antiapoptotic 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 lymphoma originate.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
burkitts-lymphoma; gene-expression; peripheral-blood; hodgkins-disease; cre recombinase; in-vivo; reactivation; apoptosis; bcr; membrane-protein-1
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Journal
Blood
Quellenangaben
Volume: 110,
Issue: 10,
Pages: 3715-3721
Publisher
American Society of Hematology
Reviewing status
Peer reviewed
Institute(s)
Research Unit Gene Vector (AGV)