Activation and targeting of immunoglobulin switch recombination by activities induced by EBV infection.
EBV is strongly associated with Burkitt's lymphoma, a B cell malignancy. In certain types of Burkitt's lymphoma, the c-myc gene has undergone translocation to the S regions associated with heavy chain switch recombination. It has not been established whether EBV infection induces recombination activities, which in turn promote translocation of c-myc, or whether translocation precedes viral infection and provides a growth advantage that is further enhanced by factors encoded or induced by the virus. To distinguish between these possibilities, we have compared the level of switch recombination activities in the EBV-negative lymphoma, BJAB, and in its EBV-infected derivative, BJAB-B1, in experiments that assayed recombination of an extrachromosomal switch substrate during transient transfection. We have found that BJAB-B1 and other EBV-positive B cell lines supported high levels of recombination of switch substrates, to produce junctions like those found in products of chromosomal switch recombination. In contrast, BJAB did not support comparable levels of switch substrate recombination. In EBV-positive B cell lines, the ability to support switch substrate recombination correlated with levels of LR1, a B cell-specific factor which is a transcriptional regulator of c-myc and which also appears to function in switch recombination. Our observations support the hypothesis that EBV infection can induce activities that affect switch recombination and thus contribute to the translocations of c-myc to the S regions that characterize certain classes of lymphomas.
Li
M J
MJ
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
Maizels
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D000276:Adjuvants, Immunologic / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D018390:Gene Targeting; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D016393:Lymphoma, B-Cell; D011995:Recombination, Genetic / Q000276:immunology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; C484201:LR1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors