Hodgkin and Reed-Sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription
Hodgkin and Reed-Sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription
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DOI：
10.1182/blood.v95.4.1443.004k55_1443_1450
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发表时间：
2000-02-15
期刊：
影响因子：
20.3
通讯作者：
Stein, H
中科院分区：
文献类型：
--
作者：
Marafioti, T;Hummel, M;Stein, H
单细胞研究旨在阐明经典霍奇金病（HD）的霍奇金细胞和Reed-Sternberg （HRS）细胞的性质和克隆性，迄今为止产生了相互矛盾的结果。采用改进的单细胞程序，分析了25例缺乏B和t细胞抗原的结节性硬化性HD患者的HRS细胞，有无Epstein-Barr病毒感染，是否存在免疫球蛋白（Ig）基因重排。1例HD患者2年后发展为滤泡性淋巴瘤。这两种淋巴瘤都起源于一个共同的前体，即生发中心B细胞。数据显示，除一例外，所有被调查的病例都含有重排的Ig基因，这些基因在所有情况下都是克隆的，并且携带了大量的体细胞突变。24例重排中有18例（75%）保留了Ig编码能力。然而，在HRS细胞中，除了1例肿瘤细胞中有Ig kappa轻链表达外，未检测到Ig信使RNA的表达。通过对HD细胞株L428和KM-HP的瞬时转染实验，证实了HRS细胞中Ig基因转录缺失。与5个对照b细胞系相比，Ig启动子/增强子报告子结构在这些细胞中几乎没有活性。我们得出结论：(1)经典HD在大多数情况下是一种b细胞淋巴瘤，(2)HRS细胞无一例外是克隆的，(3)它们来源于生发中心b细胞，(4)大多数缺乏致残突变，但(5)由于Ig基因调控元件的功能缺陷，一直失去其Ig基因转录能力。(C) 2000年由美国血液学会出版。
Single cell studies aimed at clarifying the nature and clonality of Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's disease (HD) have so far produced conflicting results. Using an improved single cell procedure, the HRS cells of 25 patients with nodular sclerosing HD lacking B- and T-cell antigens, with and without Epstein-Barr virus infection, were analyzed for the presence of immunoglobulin (Ig) gene rearrangements. One patient with HD developed follicular lymphoma 2 years later. Both lymphomas originated from a common precursor identified as a germinal center B cell. The data show that all but one of the investigated cases harbored rearranged Ig genes, which were clonal in all instances and carried a high load of somatic mutations. The Ig coding capacity was preserved in 18 of the 24 cases (75%) with rearrangements. However, expression of Ig messenger RNA was not detectable in the HRS cells with the exception of Ig kappa light chain expression in some tumor cells of 1 case. The lack of Ig gene transcription in HRS cells was confirmed by analyzing the HD cell lines L428 and KM-HP in transient transfection experiments. An Ig promoter/enhancer reporter construct showed virtually no activity in these cells compared to 5 control B-cell lines. We conclude that (1) classical HD is a B-cell lymphoma in most instances, (2) HRS cells are clonal without any exception, (3) they are derived from germinal center B-cells that (4) mostly lack crippling mutations but (5) have consistently lost their Ig gene transcription ability, due to functional defects in the Ig gene regulatory elements. (C) 2000 by The American Society of Hematology.