B-Myb overexpression results in activation and increased Fas/Fas ligand-mediated cytotoxicity of T and NK cells

The human B-myb gene encodes a transcriptional regulator that plays an impo rtant role in cell cycle progression, differentiation, and survival. To ass ess the in vivo role of B-myb, we investigated the phenotype of mouse trans genic lines in which B-Myb expression in lymphoid tissues was driven by the LCK proximal promoter. Overexpression of B-Myb had no measurable effect on the subsets of splenic and thymic lymphocytes, but was associated with inc reased expression of Fas ligand in NK and T cells. B-Myb-overexpressing spl enocytes expressed higher IFN-gamma levels and contained higher percentages of cytokine-producing cells than wild-type (wt) splenocytes, as detected b y Western blot analysis and ELISPOT assays, respectively. Ex vivo-cultured transgenic thymocytes and splenocytes had decreased survival compared with the corresponding cells from wt mice, possibly dependent on increased expre ssion of Fas ligand. In addition, Fas ligand-dependent cytotoxicity of tran sgenic T and NK cells was significantly higher than that mediated by their wt counterparts. Together, these results indicate that B-Myb overexpression results in T and NK cell activation and increased cytotoxicity. Therefore, in addition to its well-established role in proliferation and differentiat ion, B-myb also appears to be involved in activation of NK and T cells and in their regulation of Fas/Fas ligand-mediated cytotoxicity The Journal of Immunology, 2001, 167: 242-249.