VavP-Bcl2 transgenic mice develop follicular lymphoma preceded by germinal center hyperplasia
Details
Publication Year 2004-03-15,Volume 103,Issue #6,Page 2276-2283
Journal Title
BLOOD
Publication Type
Journal 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 (Emu) 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 Emu-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 Emu-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. (C) 2004 by The American Society of Hematology.
Publisher
AMER SOC HEMATOLOGY
Keywords
MUTATIONAL HOT-SPOTS; FAMILY MEMBER BIM; CENTER B-CELLS; REDUCES PROLIFERATION; AUTOANTIBODY ACTIVITY; BCL-2 EXPRESSION; SOMATIC MUTATION; GENE-EXPRESSION; IN-VIVO; T-CELLS
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2004-03-15 12:00:00
An error has occurred. This application may no longer respond until reloaded. Reload 🗙