*UCLA AIDS Institute, Los Angeles, CA; †The Institution of Viral disease Control and Prevention, CDC, Beijing, China; ‡Departments of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA; §Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL; ‖Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA; ¶Department of Epidemiology, UCLA Jonathan and Karin Fielding School of Public Health, Los Angeles, CA; and #Jonsson Comprehensive Cancer Center, Los Angeles, CA.
J Acquir Immune Defic Syndr. 2013 Oct 1;64(2):204-10. doi: 10.1097/QAI.0b013e31829d4d50.
AIDS-related non-Hodgkin lymphoma (AIDS-NHL) is a common AIDS-defining cancer. Prior studies suggest that chronic B-cell activation precedes AIDS-NHL diagnosis. Activation of B cells by multiple factors, including Toll-like receptor (TLR) signaling, leads to the expression of activation-induced cytidine deaminase (AID), a DNA mutating molecule that can contribute to oncogene translocations/mutations, leading to NHL. The goal of this study was to determine whether surface markers expressed on activated and/or germinal center B cells, and AID expression, were elevated on circulating B cells preceding AIDS-NHL and to determine if TLR signaling contributes to this activated B-cell phenotype.
Stored viable peripheral blood mononuclear cell specimens, obtained before AIDS-NHL diagnosis, were assessed by multicolor flow cytometry. Additionally, B cells isolated from peripheral blood mononuclear cell were exposed to TLR ligands in vitro, after which B-cell phenotype was assessed by flow cytometry.
An elevated fraction of B cells expressing CD10, CD71, or CD86 was seen in those who went on to develop AIDS-NHL. AID expression was detected in some who developed AIDS-NHL, but not in HIV+ or HIV- controls. TLR2-stimulated purified B cells exhibited the activated B-cell phenotype observed in HIV+ subjects before AIDS-NHL diagnosis.
These results indicate that an elevated fraction of B cells display an activated/germinal center phenotype in those HIV+ subjects who go on to develop AIDS-NHL and suggest that TLR2-mediated activation may play a role in HIV infection-associated B-cell activation, potentially contributing to the genesis of AIDS-NHL.
艾滋病相关非霍奇金淋巴瘤（AIDS-NHL）是一种常见的艾滋病定义性癌症。先前的研究表明，B 细胞的慢性激活先于 AIDS-NHL 的诊断。多种因素（包括 Toll 样受体（TLR）信号）激活 B 细胞，导致激活诱导胞苷脱氨酶（AID）的表达，AID 是一种导致 NHL 的致癌基因易位/突变的 DNA 突变分子。本研究的目的是确定在 AIDS-NHL 之前，循环 B 细胞上是否表达了激活和/或生发中心 B 细胞的表面标志物，以及 AID 表达是否升高，以及 TLR 信号是否有助于这种激活的 B 细胞表型。
通过多色流式细胞术评估 AIDS-NHL 诊断前获得的储存可存活外周血单核细胞标本。此外，从外周血单核细胞中分离出 B 细胞，在体外暴露于 TLR 配体后，通过流式细胞术评估 B 细胞表型。
在那些继续发展为 AIDS-NHL 的人中，表达 CD10、CD71 或 CD86 的 B 细胞分数升高。在一些发展为 AIDS-NHL 的人中检测到 AID 表达，但在 HIV+或 HIV-对照中未检测到。TLR2 刺激的纯化 B 细胞表现出在 AIDS-NHL 诊断前 HIV+患者中观察到的激活的 B 细胞表型。
这些结果表明，在那些继续发展为 AIDS-NHL 的 HIV+患者中，B 细胞的一部分表现出激活/生发中心表型，并且表明 TLR2 介导的激活可能在 HIV 感染相关的 B 细胞激活中起作用，可能有助于 AIDS-NHL 的发生。
