Frequent expansion of Epstein–Barr virus (EBV) infected cells in germinal centres of tonsils from an area with a high incidence of EBV‐associated lymphoma
Frequent expansion of Epstein–Barr virus (EBV) infected cells in germinal centres of tonsils from an area with a high incidence of EBV‐associated lymphoma
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DOI：
10.1002/(sici)1096-9896(199902)187:3
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发表时间：
1999-02
期刊：
影响因子：
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通讯作者：
I. Araújo;H. Foss;M. Hummel;I. Anagnostopoulos;H. Barbosa;Achilea C Bittencourt;H. Stein
中科院分区：
文献类型：
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作者：
I. Araújo;H. Foss;M. Hummel;I. Anagnostopoulos;H. Barbosa;Achilea C Bittencourt;H. Stein
伯基特淋巴瘤（BL）和霍奇金病（HD）发生在发展中地区，经常与EB病毒（EBV）感染有关，并在儿童期发病率很高。最近的基因分型研究表明，这两种肿瘤的肿瘤细胞代表含有体细胞突变的免疫球蛋白重链基因的B细胞。这意味着这些肿瘤的前体参与了生殖中心（GC）反应。因此，我们推测，与生活在工业化国家的儿童相比，生活在发展中地区的儿童的正常淋巴组织将在GC中含有更多的EBV感染细胞。为了验证这一假设，分别通过原位杂交和免疫组织学分析了来自巴伊亚（巴西）的40名儿童和来自德国儿童的增生性扁桃体中EBV编码的小核RNA（EBER）和EBV编码的蛋白的存在。尽管两组的总体EBV感染率相似，（50%的巴伊亚人对45%的德国病例），在来自巴西的8/20例EBV阳性扁桃体的GC中发现了显著更高数量的EBER阳性淋巴样细胞（9-89个细胞/GC;平均：14.5个细胞/GC/例），而来自德国的18个扁桃体中仅3个显示少量EBER阳性细胞（1-9个细胞/GC;平均值：每例0.5个细胞/GC）（p <0.007）。此外，巴伊亚样本中EBV感染的GC细胞类似于中心母细胞，表现出有丝分裂活性，并且在两例病例中显示EBV编码的潜伏膜蛋白（LMP）-1表达，这在德国样本中不存在。这些数据表明，潜伏性EBV感染的细胞在发展中地区比工业化国家更频繁地参与GC反应，并且可能异常表达致癌蛋白LMP-1。这可以部分解释在该区域EBV与GC细胞或其后代相关的淋巴瘤（如BL和HD）相关的发病率较高。版权所有© 1999年约翰威利父子有限公司。
Burkitt's lymphoma (BL) and Hodgkin's disease (HD) occurring in developing regions are frequently associated with Epstein–Barr virus (EBV) infection and have a high incidence in childhood. Recent genotyping studies indicate that the tumour cells of both neoplasms represent B cells that contain somatically mutated immunoglobulin heavy chain genes. This implies that the precursors of these neoplasms have participated in the germinal centre (GC) reaction. We therefore presumed that normal lymphoid tissues from children living in developing regions would harbour an increased number of EBV‐infected cells within the GC, when compared with children living in industrialized nations. To test this hypothesis, hyperplastic tonsils from 40 children living in Bahia (Brazil) and 40 from German children were analysed for the presence of EBV‐encoded small nuclear RNA (EBER) and EBV‐encoded proteins by in situ hybridization and immunohistology, respectively. Although the overall EBV infection rate was similar in both groups (50 per cent of Bahian vs. 45 per cent of German cases), a significantly higher number of EBER‐positive lymphoid cells were found in the GCs of 8/20 EBV‐positive tonsils from Brazil (9–89 cells/GC; mean: 14·5 cells/GC per case), while only 3/18 tonsils from Germany displayed a few EBER positive cells (1–9 cells/GC; mean: 0·5 cell/GC per case) in this compartment (p < 0·007). In addition, the EBV‐infected GC cells in Bahian samples resembled centroblasts, exhibited mitotic activity, and in two cases showed expression of EBV‐encoded latent membrane protein (LMP)‐1, findings not present in German samples. These data show that latently EBV‐infected cells participate more frequently in GC reactions in developing regions than in industrialized countries and may abnormally express the oncogenic protein LMP‐1. This could in part explain the higher incidence in this region of EBV association with lymphomas related to GC cells or their progeny, such as BL and HD. Copyright © 1999 John Wiley & Sons, Ltd.