LMP2A Modulation of B cell Survival and Activation

描述（由申请方提供）：长期目标是了解EB病毒（EBV）潜伏膜蛋白2A（LMP 2A）在维持B细胞中EBV潜伏期中的作用。本研究的目的是确定LMP 2A是否改变体内B细胞的存活和功能。基于先前的数据，本研究的假设是LMP 2A在携带Ig的B细胞中发出信号以抑制B细胞活化，同时促进体内B细胞存活。为了检验这一假设，将进行以下目的：（1）确定LMP 2A是否在存在或不存在抗原的情况下延长Ig-珠化B细胞的体内存活。(2)确定LMP 2A是否抑制自身抗原诱导的携带Ig的B细胞中的BCR信号传导。(3)确定LMP 2A是否在体内和体外抑制B细胞响应抗原的功能。通过将在B细胞中表达LMP 2A的转基因小鼠与产生具有对鸡蛋溶菌酶（HEL）特异性的BCR的B细胞的小鼠杂交，我们已经产生了一种新的系统来测试LMP 2A是否改变体内B细胞的存活和活化。将使用BrdU标记、FACS分析、抗体应答和蛋白质印迹分析来确定LMP 2A是否改变携带Ig的B细胞的半衰期和活化。这些研究可能为根除恶性肿瘤前B细胞中EBV潜伏感染的治疗提供理论基础。

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.