Bcl-2 reduces lymphomagenesis in ΔV-TCRβ transgenic mice

Abstract

Overexpression of the bcl-2 oncogene in the lymphoid compartment of transgenic mice prolongs the lifespan of lymphocytes and leads to a low incidence of lymphomas at later age. Transgenic mice carrying a mutated T-cell receptor lacking the variable domain (ΔV-TCRβ) suffer from lymphocyte depletion and are highly predisposed to lymphoma development. We intercrossed Bcl-2-Ig and ΔV-TCRβ transgenic mice to assess whether Bcl-2 could synergize with ΔV-TCRβ in tumorigenesis as reported previously for other oncogenes. Surprisingly, bitransgenic ΔV-TCRβ; bcl-2-Ig mice showed a reduction in the incidence of lymphomas. Analyses of prelymphomatous mice showed that Bcl-2 restored some of the phenotypic aberrations caused by the ΔV-TCRβ transgene in the lymphoid compartment. The inhibitory activity of Bcl-2 on ΔVTCRβ-induced lymphomagenesis was not observed when both transgenes were crossed into the RAG-1^−/− background suggesting an important role for more mature lymphocytes in this phenomenon. These results show that, depending on the specific conditions, overexpression of Bcl-2 can both promote as well as impair lymphoma development.