Impact of Human T-cell Leukemia Virus-1 and Epstein-Barr Virus Infections on B-cell Lymphoma and Adult T-cell Leukemia/Lymphoma Developments. Homo sapiens

We established HTLV-1/EBV co-infected cell lines from Adult T-cell Leukemia/Lymphoma (ATLL) patients, and found that they are derived from germinal center (GC) B-cells or transitional B-cells between GC-B-cells and memory B-cells by using gene expression profiling (GEP) analysis. Expression of CD25 and TSLC1, which are diagnostic markers of ATLL cells, were identified in the ATLL-derived B-cell lines as discriminators of EBV-imortalized cell lines, indicating that HTLV-1 infection leads to express CD25 and TSLC1. Overall design: The three cell lines LMY3B, OATL9 and LHM115 represent three independent B cell lines established by isolating peripheral blood from three different HTLV-1+ patients. Primary naïve, GC and memory B-cells were selected to identify the derivation of ATLL-derived B-cell lines, and diffuse large B-cell lymphoma cell lines and EBV-immortalized cell lines were used to characterize tumorigenicity of ATLL-derived B-cell lines.

我们从成人T细胞白血病/淋巴瘤（Adult T-cell Leukemia/Lymphoma, ATLL）患者体内建立了人类T淋巴细胞病毒I型（HTLV-1）与EB病毒（EBV）共感染细胞系，并借助基因表达谱（gene expression profiling, GEP）分析发现，这些细胞系起源于生发中心B细胞（germinal center B-cell, GC B细胞），或是介于生发中心B细胞与记忆B细胞之间的过渡型B细胞。CD25与TSLC1作为ATLL细胞的诊断标志物，在ATLL来源的B细胞系中被鉴定为可区分EB病毒永生化细胞系的特征标志物，这提示HTLV-1感染可诱导CD25与TSLC1的表达。整体实验设计如下：细胞系LMY3B、OATL9与LHM115为三株独立的B细胞系，均通过分离三名不同HTLV-1阳性患者的外周血构建得到。我们选取原代初始B细胞、生发中心B细胞与记忆B细胞，以鉴定ATLL来源B细胞系的细胞起源；同时以弥漫大B细胞淋巴瘤细胞系及EB病毒永生化细胞系作为参照，表征ATLL来源B细胞系的致瘤特性。