Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation.
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.
Yang
Xuwei
X
Hart and Louise Lyon Immunology Laboratory, Division of Clinical Immunology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095-1680, USA.
Lee
Koutetsu
K
Said
Jonathan
J
Gong
Xun
X
Zhang
Ke
K
D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002678:Chimera / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6; D011519:Proto-Oncogenes; D014158:Transcription, Genetic; D014178:Translocation, Genetic
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6; D004247:DNA