Viral latent membrane protein 1 (LMP-1)-induced CD99 down-regulation in B cells leads to the generation of cells with Hodgkin's and Reed-Sternberg phenotype.
Viral latent membrane protein 1 (LMP-1)-induced CD99 down-regulation in B cells leads to the generation of cells with Hodgkin's and Reed-Sternberg phenotype.
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DOI：
10.1182/blood.v95.1.294.001k15_294_300
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发表时间：
2000
期刊：
影响因子：
20.3
通讯作者：
Soon Ha Kim;Y. Shin;I. Lee;Y. Bae;H. Sohn;Young Ho Suh;H. Ree;M. Rowe;S. Park
中科院分区：
文献类型：
--
作者：
Soon Ha Kim;Y. Shin;I. Lee;Y. Bae;H. Sohn;Young Ho Suh;H. Ree;M. Rowe;S. Park
最近我们报道，CD99(Mic2)的下调是霍奇金病中霍奇金和里德-斯特恩伯格(H-RS)细胞产生的主要条件。在本研究中，我们提供的证据表明，CD99的下调是由EB病毒(EBV)潜伏膜蛋白1(LMP-1)的高表达所诱导的，LMP-1在EBV相关性霍奇金病的H-RS细胞中高表达。为了研究LMP-1在体外对CD99表达的影响，我们将SV40早期启动子驱动的LMP-1表达载体导入肿瘤淋巴母细胞B细胞系IM9，建立了一个稳定的细胞系，该细胞株中内源性LMP-1的表达水平几乎可以忽略不计。在该细胞系中，LMP-1过表达导致CD99表达下调，H-RS细胞的形态和功能特征与霍奇金病患者的淋巴组织和CD99缺陷的B细胞难以区分。此外，在EBV阴性的B细胞克隆BJAB中诱导LMP-1表达，直接导致表面CD99表达下调。Northern和Western分析数据表明，LMP-1的过表达对CD99的表达产生了负面影响，这一结果得到了CD99启动子驱动的荧光素酶启动子报告结构体在共表达LMP-1时下调的实验的支持。因此，我们的数据有力地表明，EBV LMP-1蛋白通过转录调控在CD99的下调中发挥关键作用，从而导致H-RS细胞的产生。(血。2000；95：294-300)
Recently we reported that the down-regulation of CD99 (Mic2) is a primary requirement for the generation of Hodgkin's and Reed-Sternberg (H-RS) cells seen in Hodgkin's disease. In this study, we provide evidence that the down-regulation of CD99 is induced by high expression of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1), which is highly expressed in H-RS cells of EBV-associated Hodgkin's disease. To investigate the effect of LMP-1 on the expression of CD99 in vitro, we established a stable cell line by transfecting an SV40-early promoter driven-LMP-1 expression construct into a neoplastic lymphoblastoid B cell line, IM9, in which the level of endogenous LMP-1 expression is almost negligible. In this cell line, the overexpression of LMP-1 led to the down-regulation of CD99 and the acquisition of morphological and functional characteristics of H-RS cells indistinguishable from those in lymph nodes of Hodgkin's disease patients and in CD99-deficient B cells. In addition, induced LMP-1 expression in an EBV-negative B cell clone, BJAB, directly caused the down-regulation of surface CD99 expression. Northern and Western analysis data, showing that overexpression of LMP-1 negatively influenced the expression of CD99, were supported by experiments in which a CD99 promoter-driven luciferase promoter reporter construct transfected into 293T cells was down-regulated when LMP-1 was coexpressed. Therefore, our data strongly suggest that the EBV LMP-1 protein plays a pivotal role in the down-regulation of CD99 via transcriptional regulation, which leads to the generation of the H-RS cells. (Blood. 2000;95:294-300)