Powzaniuk M A, Trotta R, Loza M J, Harth A, Iozzo R V, Eisenlohr L C, Perussia B, Calabretta B
Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA.
J Immunol. 2001 Jul 1;167(1):242-9. doi: 10.4049/jimmunol.167.1.242.
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-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 increased expression of Fas ligand in NK and T cells. B-Myb-overexpressing splenocytes expressed higher IFN-gamma levels and contained higher percentages of cytokine-producing cells than wild-type (wt) splenocytes, as detected by 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 expression of Fas ligand. In addition, Fas ligand-dependent cytotoxicity of transgenic 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 differentiation, B-myb also appears to be involved in activation of NK and T cells and in their regulation of Fas/Fas ligand-mediated cytotoxicity
人类B-myb基因编码一种转录调节因子，其在细胞周期进程、分化及存活中发挥重要作用。为评估B-myb在体内的作用，我们研究了淋巴组织中B-Myb表达由LCK近端启动子驱动的小鼠转基因品系的表型。B-Myb的过表达对脾和胸腺淋巴细胞亚群没有可测量的影响，但与NK细胞和T细胞中Fas配体表达增加相关。通过蛋白质免疫印迹分析和ELISPOT检测分别发现，与野生型（wt）脾细胞相比，过表达B-Myb的脾细胞表达更高水平的干扰素-γ，且产生细胞因子的细胞百分比更高。与wt小鼠相应细胞相比，体外培养的转基因胸腺细胞和脾细胞存活率降低，这可能依赖于Fas配体表达增加。此外，转基因T细胞和NK细胞的Fas配体依赖性细胞毒性显著高于其wt对应细胞介导的细胞毒性。这些结果共同表明，B-Myb过表达导致T细胞和NK细胞活化及细胞毒性增加。因此，除了其在增殖和分化中已确立的作用外，B-myb似乎还参与NK细胞和T细胞的活化及其对Fas/Fas配体介导的细胞毒性的调节。
