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 receptor s (TCRs). RAGs are normally expressed during a narrow window of precur sor lymphocyte development. RAG expression was examined in Epstein-Bar r virus (EBV)-infected B cells. No steady-state RAG RNA was found in E BV immortalized cells, including newly established B lymphoblastoid ce ll lines derived from precursor lymphocytes that transcribed RAGs at t he time of infection. RAG RNAs were detected in some endemic (EBV(+)) and also in some sporadic (EBV(-)) Burkitt's lymphoma lines that had b een infected with EBV in vitro. The RAG(+), EBV(+) Burhitt's lines wer e unusual in that they were SlgM(+) (one was SlgG(+), SlgM(-)), CD10(), and lacked terminal deoxynucleotidyl transferase. In EBV(+) Burkitt 's lymphoma lines, transcription of virus latent membrane protein-1 (L MP-1) was correlated with downregulation of RAG-1 and RAG-2. Conversel y, absence of LMP-1 in clones of EBV(+) tumor lines was associated wit h increased RAG transcription. Translocation of c-mye into V(D)J loci has been observed in endemic Burkitt's lymphomas, and heptamer-nonamer recombination signal sequences have been identified at some chromosom al breakpoints. Association of RAG transcription with EBV infection ra ises the possibility that, under certain conditions, virus might predi spose to aberrant V(D)J recombination reactions. (C) 1995 by The Ameri can Society of Hematology.