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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2276-2283. Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-07-2469. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2469v1 103/6/2276    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 Egle, A. Articles by Cory, S. Search for Related Content PubMed PubMed Citation Articles by Egle, A. Articles by Cory, S. Related Collections Apoptosis Oncogenes and Tumor Suppressors Immunobiology Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA VavP-Bcl2 transgenic mice develop follicular lymphoma preceded by germinal center hyperplasia Alexander Egle, Alan W. Harris, Mary L. Bath, Lorraine O'Reilly, and Suzanne Cory From the Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. In human follicular lymphoma the t(14; 18) chromosome translocation activates the antiapoptotic oncogene Bcl2 by linking it to the immunoglobulin heavy chain (IGH) locus. Transgenic mice expressing Bcl2 controlled by an Igh enhancer (Eµ) do not develop follicular lymphoma, although they do have an increased incidence of other B-lymphoid neoplasms. We have now analyzed tumorigenesis in mice bearing a Bcl2 transgene controlled by Vav gene regulatory sequences (VavP), which confer expression in multiple hematopoietic lineages. Unlike Eµ-Bcl2 mice, many VavP-Bcl2 mice older than 10 months developed follicular lymphoma. Young VavP-Bcl2 mice had an overabundance of enlarged germinal centers and greatly elevated numbers of cycling B cells that had undergone IgH class switching and V-gene hypermutation. The peripheral T-cell compartment was larger in the VavP-Bcl2 mice than in Eµ-Bcl2 strains and, notably, CD4 T cells were 5-fold increased over normal. The germinal center hyperplasia required CD4 T cells, because it could be abolished by anti-CD4 antibody in vivo. VavP-Bcl2 mice also had a propensity to develop kidney disease of the autoimmune type. We suggest that the increased survival capacity of B and T cells fosters prolonged germinal center reactions, and that autoreactivity and hypermutation conspire to generate follicular lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: T cells in mouse follicular lymphoma Michael A. Teitell Blood 2004 103: 1981-1982. [Full Text] [PDF] This article has been cited by other articles: A. M. Unni, T. Bondar, and R. Medzhitov Intrinsic sensor of oncogenic transformation induces a signal for innate immunosurveillance PNAS, February 5, 2008; 105(5): 1686 - 1691. [Abstract] [Full Text] [PDF] M. M. Zangani, M. Froyland, G. Y. Qiu, L. A. Meza-Zepeda, J. L. Kutok, K. M. Thompson, L. A. Munthe, and B. Bogen Lymphomas can develop from B cells chronically helped by idiotype-specific T cells J. Exp. Med., May 14, 2007; 204(5): 1181 - 1191. [Abstract] [Full Text] [PDF] A. M. Glas, L. Knoops, L. Delahaye, M. J. Kersten, R. E. 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