VavP-Bcl2 transgenic mice develop follicular lymphoma preceded by germinal center hyperplasia
Year: 2003
Type: article
Abstract: 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 (E mu) 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 E mu-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 E mu-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.
Source: Blood
Authors: Alexander Egle, Alan W. Harris, Mary L. Bath, Lorraine O'Reilly, Suzanne Cory
Institution: Walter and Eliza Hall Institute of Medical Research
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Role of Bcl-2 family members, Bcl-2 and Bim, in B-lymphomagenesis and autoimmunity in transgenic and knockout animal models, How cell death is controlled, influences normal development and contributes to cancer and other diseases, ONCOGENE INDUCED LEUKEMOGENESIS IN TRANGENIC MICE, The physiologic roles of death receptor-controlled cell death pathways within the myeloid and erythroid haematopoiesis in transgenic mouse models
OpenAlex ID: W2072719177