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 important role in cell cycle progression, differentiation,and survival. To assess the in vivo role of B-myb, we investigated the phenotype of mouse transgenic lines in which B-Mybexpression in lymphoid tissues was driven by the LCK proximal promoter. Overexpression of B-Myb had no measurable effect onthe subsets of splenic and thymic lymphocytes, but was associated with increased expression of Fas ligand in NK and T cells.B-Myb-overexpressing splenocytes expressed higher IFN-␥ levels and contained higher percentages of cytokine-producing cellsthan wild-type (wt) splenocytes, as detected by Western blot analysis and ELISPOT assays, respectively. Ex vivo-cultured trans-genic thymocytes and splenocytes had decreased survival compared with the corresponding cells from wt mice, possibly dependenton increased expression of Fas ligand. In addition, Fas ligand-dependent cytotoxicity of transgenic T and NK cells was significantlyhigher than that mediated by their wt counterparts. Together, these results indicate that B-Myb overexpression results in T andNK cell activation and increased cytotoxicity. Therefore, in addition to its well-established role in proliferation and differentiation,B-myb also appears to be involved in activation of NK and T cells and in their regulation of Fas/Fas ligand-mediatedcytotoxicity