Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation.
Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation.
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DOI：
10.1182/blood-2006-03-011536
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发表时间：
2006-09
期刊：
影响因子：
20.3
通讯作者：
Xuwei Yang;Koutetsu Lee;J. Said;Xun Gong;K. Zhang
中科院分区：
文献类型：
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作者：
Xuwei Yang;Koutetsu Lee;J. Said;Xun Gong;K. Zhang
免疫球蛋白（IG）基因和BCL 6原癌基因之间的染色体易位（CT）通常与弥漫性大B细胞淋巴瘤（DLBCL）和滤泡性淋巴瘤（FL）相关，并与这些淋巴瘤的发生有关。然而，IG/BCL 6易位本身是否足以驱动恶性转化尚不清楚。为了了解IG/BCL 6易位细胞在其恶性转化之前的生物学，我们开发了一种能够通过检测反映相互Igmu/BCL 6易位的嵌合Imu-BCL 6 E2和BCL 6 E1-Cmu 1转录物来检测100万个混合细胞中的1至3个Igmu/BCL 6 CT细胞的系统。存在于绝大多数正常淋巴组织中的嵌合转录物是由于Igmu/BCL 6 CT而不是由反式剪接产生的。Imu-BCL 6 E2和BCL 6 E1-Cmu 1转录物在相同的细胞群中共表达。从表达Imu-BCL 6转录物的B细胞亚群中分离IG/BCL 6重组连接本身。Igmu/BCL 6 CT的出现与表达生发中心的细胞相关，但与幼稚B细胞标志物无关。该研究表明，IG/BCL 6易位发生在健康人的生发中心期B细胞中，并且IG/BCL 6 CT本身不太可能足以引起人B细胞的恶性转化。
Chromosomal translocations (CTs) between immunoglobulin (Ig) genes and the BCL6 proto-oncogene are frequently associated with diffuse large B-cell lymphomas (DLBCLs) and follicular lymphomas (FLs) and are implicated in the development of these lymphomas. However, whether Ig/BCL6 translocation per se is sufficient to drive malignant transformation is not clear. To understand the biology of Ig/BCL6-translocated cells prior to their malignant transformation, we developed a system capable of detecting 1 to 3 Igmu/BCL6 CT cells in 1 million mixed cells through the detection of chimeric Imu-BCL6E2 and BCL6E1-Cmu1 transcripts that reflect reciprocal Igmu/BCL6 translocations. The chimeric transcripts that existed in the vast majority of normal lymphoid tissues are due to Igmu/BCL6 CT and were not generated from trans-splicing. Both Imu-BCL6E2 and BCL6E1-Cmu1 transcripts were coexpressed in the same cell populations. The Ig/BCL6 recombination junctions themselves were isolated from B-cell subpopulations expressing the Imu-BCL6 transcripts. The appearance of Igmu/BCL6 CT was associated with cells expressing germinal center but not naive B-cell markers. This study shows that Ig/BCL6 translocations occur in germinal center-stage B cells in healthy humans, and that Ig/BCL6 CTs per se are not likely sufficient to cause the malignant transformation in the context of human B cells.