LMP2A Modulation of B cell Survival and Activation

描述(由申请人提供)：长期目标是了解EB病毒潜伏膜蛋白2A(LMP2A)在维持B细胞中EBV潜伏期中的作用。这项研究的目标是确定LMP2A是否改变了体内B细胞的存活和功能。根据以前的数据，本研究的假设是LMP2A信号在携带Ig的B细胞中抑制B细胞的激活，同时促进B细胞在体内的存活。为了验证这一假说，将进行以下目的：(1)确定在没有或存在抗原的情况下，LMP2A是否延长了体内Ig结合B细胞的存活。(2)检测LMP2A是否抑制自身抗原诱导的免疫球蛋白B细胞BCR信号转导。(3)测定LMP2A在体内和体外是否抑制B细胞对抗原的反应。通过将在B细胞中表达LMP2A的转基因小鼠与产生B细胞的小鼠进行杂交，并使用针对鸡蛋溶菌酶(HEL)的BCR，我们产生了一种新的系统来测试LMP2A是否改变了体内B细胞的存活和激活。BrdU标记、FACS分析、抗体反应和Western Blot分析将被用来确定LMP2A是否改变了携带Ig的B细胞的半衰期和激活。这些研究可能为治疗人员根除恶性肿瘤前B细胞中的EBV潜伏感染提供理论依据。

DESCRIPTION(provided by applicant): The long-term goal of is to understand the role of Epstein-Barr Virus (EBV) latent membrane protein 2A (LMP2A) in maintaining EBV latency in B cells. The goal of this study is to determine if LMP2A alters B cell survival and function in vivo. Based on previous data, the hypothesis for this study is that LMP2A signals in Ig-bearing B cells to inhibit B cell activation, while promoting B cell survival in vivo. To test this hypothesis, the following aims will be performed: (1) Determine if LMP2A extends the survival of Ig-beadng B cells in vivo in the absence or presence of antigen. (2) Determine if LMP2A inhibits BCR signaling in Ig-bearing B cells induced by autoantigen. (3) Determine if LMP2A inhibits the function of B cells in response to antigen in vivo and in vitro. By crossing transgenic mice that express LMP2A in B cells to mice that produce B cells with BCR specific for hen-egg lysozyme (HEL), we have generated a novel system to test if LMP2A alters B cell survival and activation in vivo. BrdU-labeling, FACS analysis, antibody responses and Western Blot analysis will be utilized to determine if LMP2A alters the half life and activation of Ig-bearing B cells. These studies may provide rationales for therapeutics to eradicate EBV latent infection in B cells that precedes malignant tumors.