Expression of recombination activating genes (RAG-1 and RAG-2) in Epstein-Barr virus-bearing B cells.
Recombination activating genes 1 and 2 (RAG-1 and RAG-2), are the only lymphoid-specific genes required for the site-directed recombination reaction leading to generation of B-cell receptors and T-cell receptors (TCRs). RAGs are normally expressed during a narrow window of precursor lymphocyte development. RAG expression was examined in Epstein-Barr virus (EBV)-infected B cells. No steady-state RAG RNA was found in EBV immortalized cells, including newly established B lymphoblastoid cell lines derived from precursor lymphocytes that transcribed RAGs at the time of infection. RAG RNAs were detected in some endemic (EBV+) and also in some sporadic (EBV-) Burkitt's lymphoma lines that had been infected with EBV in vitro. The RAG+, EBV+ Burkitt's lines were unusual in that they were SIgM+ (one was SIgG+, SIgM-), CD10+, and lacked terminal deoxynucleotidyl transferase. In EBV+ Burkitt's lymphoma lines, transcription of virus latent membrane protein-1 (LMP-1) was correlated with downregulation of RAG-1 and RAG-2. Conversely, absence of LMP-1 in clones of EBV+ tumor lines was associated with increased RAG transcription. Translocation of c-myc into V(D)J loci has been observed in endemic Burkitt's lymphomas, and heptamer-nonamer recombination signal sequences have been identified at some chromosomal breakpoints. Association of RAG transcription with EBV infection raises the possibility that, under certain conditions, virus might predispose to aberrant V(D)J recombination reactions.
Laboratory of Infectious Diseases, Dana-Farber Cancer Institute, Boston, MA 02115.
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Kuhn-Hallek
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Sage
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Stein
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Groelle
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Fingeroth
D001402:B-Lymphocytes / Q000821:virology*; D002051:Burkitt Lymphoma / Q000473:pathology / Q000821:virology; D002461:Cell Line, Transformed; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004268:DNA-Binding Proteins; D015967:Gene Expression Regulation, Viral; D015322:Gene Rearrangement, B-Lymphocyte; D006566:Herpesviridae Infections / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis*; D011995:Recombination, Genetic; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000473:pathology; D045567:VDJ Recombinases; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics
D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018398:Homeodomain Proteins; D009856:Oncogene Proteins, Viral; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2; D014763:Viral Matrix Proteins; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases