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Blood, 15 September 2006, Vol. 108, No. 6, pp. 2006-2012.
Prepublished online as a Blood First Edition Paper on May 25, 2006; DOI 10.1182/blood-2006-03-011536.


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NEOPLASIA

Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation

Xuwei Yang, Koutetsu Lee, Jonathan Said, Xun Gong, and Ke Zhang

From the Hart and Louise Lyon Immunology Laboratory, Division of Clinical Immunology/Allergy, Department of Medicine, and Department of Pathology, David Geffen School of Medicine at University of California–Los Angeles (UCLA), and Fujian Union Hospital, Fujian Medical University, Fuzhou, Fujian, the People's Republic of China.

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 Igµ/BCL6 CT cells in 1 million mixed cells through the detection of chimeric Iµ-BCL6E2 and BCL6E1-Cµ1 transcripts that reflect reciprocal Igµ/BCL6 translocations. The chimeric transcripts that existed in the vast majority of normal lymphoid tissues are due to Igµ/BCL6 CT and were not generated from trans-splicing. Both Iµ-BCL6E2 and BCL6E1-Cµ1 transcripts were coexpressed in the same cell populations. The Ig/BCL6 recombination junctions themselves were isolated from B-cell subpopulations expressing the Iµ-BCL6 transcripts. The appearance of Igµ/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.


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