Submitted March 21, 2006
Accepted May 8, 2006
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*
Department of Medicine, David Geffen School of Medicine at UCLA
Department of Pathology, David Geffen School of Medicine at UCLA
* Corresponding author; email: kzhang{at}mednet.ucla.edu.
Chromosomal translocations (CT) between immunoglobulin (Ig) genes and the BCL6 proto-oncogene are frequently associated with diffuse large B cell lymphomas (DLBCL) and follicular lymphomas (FL) 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 1-3 Igµ/BCL6 CT cells in one million mixed cells through the detection of chimeric Im-BCL6E2 and BCL6E1-Cm1 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 co-expressed 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 normal humans, and that Ig/BCL6 CTs per se are not likely sufficient to cause the malignant transformation in the context of human B cells.
