STATE OF B CELL DIFFERENTIATION AND EBV GENE EXPRESSION

这项研究项目的主要目标是1)识别EBV基因， 有助于B细胞在体外永生化和与EBV相关 体内淋巴肿大，以及2)研究可能的相互作用 EBV与选定的细胞基因(c-FGR原癌基因和CD23)之间的关系 自分泌B细胞生长因子)，以及3)评估B细胞的影响 分化对EB病毒诱导的B细胞增殖的影响为了实现我们的目标 目标，处于不同分化阶段的恶性B细胞 感染全病毒或将被选中的基因导入 (EBNA2，LMP，CD23)以确定与B细胞有关的基因 永生化及EBV基因在鼠脑中的差异表达研究 分化的早期和晚期。这些基因被选为 最有可能永垂不朽的部分原因是， 我们在携带EBV的人类体内发现了高水平的转录 淋巴瘤。我们假设1)一个或多个病毒基因的表达 (可能是EBNA2或LMP)允许在体外永久生长，并可能有助于 2)EBV对B细胞生长的影响可能是 通过细胞基因c-FGR和/或CD23介导；3)B细胞 分化对EBV潜伏基因表达及预后的影响 EB病毒感染。这些实验将在指导下进行 南希·拉布-特劳布博士，一位老牌的EBV研究人员，在 EB病毒感染的分子分析。拟议的临床研究 将由肿瘤学主任霍华德·奥泽尔医学博士和丹尼斯监督 W.Ross医学博士，诺斯大学血液病理学主任 在教堂山的卡罗莱纳。

The major goals of this research project are 1) To identify EBV genes that contribute to B cell immortalization in vitro and to EBV-related lymphomagenesis in vivo, and 2) To investigate possible interactions between EBV and selected cellular genes (c-fgr protooncogene and CD23 autocrine B cell growth factor), and 3) To assess the influence of B cell differentiation on EBV-induced B cell proliferation. To accomplish our goals, malignant B cells at varying stages of differentiation will be infected with whole virus or will be transfected with selected genes (EBNA2, LMP, CD23) to identify genes that are responsible for B cell immortalization and to study the differential expression of EBV genes in early versus late stages of differentiation. These genes were chosen as most likely to immortalize based, in part, on a preliminary experiment in which we discovered high levels of transcription in an EBV-containing human lymphoma. We hypothesize that 1) Expression of one or more viral genes (possibly EBNA2 OR LMP) permit permanent growth in vitro and may contribute to viral oncogenesis in vivo; 2) EBV's effect on B cell growth could be mediated through the cellular genes c-fgr and/or CD23; and 3) B cell differentiation influences expression of EBV latent genes and outcome of EBV infection. These experiments will be carried out under the direction of Nancy Raab-Traub PhD, an established EBV researcher with expertise in molecular analysis of EBV infection. The proposed clinical investigations will be supervised by Howard Ozer MD PhD, Director of Oncology, and Dennis W. Ross MD PhD, Director of Hematopathology at the University of North Carolina at Chapel Hill.