STATE OF B CELL DIFFERENTIATION AND EBV GENE EXPRESSION

本研究项目的主要目标是：1）鉴定EBV基因， 有助于体外B细胞永生化和EBV相关的 体内淋巴瘤发生，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CD 23）之间的关系 自分泌B细胞生长因子），以及3）评估B细胞生长因子的影响 分化对EBV诱导的B细胞增殖的影响。 完成我们 为了达到这一目的，将在不同分化阶段的恶性B细胞中， 感染整个病毒或将被选定的基因转染 （EBNA 2、LMP、CD 23）以鉴定负责B细胞增殖的基因。 研究EB病毒基因在人胚肺组织中的差异表达， 分化的早期和晚期阶段。 这些基因被选为 最有可能永生的部分原因是， 我们在携带EB病毒的人类中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EBNA 2或LMP）允许体外永久生长，并可能有助于 2）EBV对B细胞生长的影响可能与EBV对细胞增殖的影响有关。 通过细胞基因c-fgr和/或CD 23介导;和3）B细胞 分化影响EB病毒潜伏基因的表达和预后 EB病毒感染。 这些实验将在 Nancy Raab-Traub博士，一位成熟的EBV研究人员， EBV感染的分子分析。 拟定的临床研究 将由肿瘤学主任霍华德奥泽医学博士和丹尼斯监督 W. Ross医学博士，北方大学血液病理学主任 查佩尔山的卡罗莱纳。

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.