• Malgorzata Cebrat, Arkadiusz Miazek, and Pawel Kisielow.
• Department of Tumor Immunology, Laboratory of Transgenesis and Lymphocyte Biology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
• Eur. J. Immunol. 2005 Jul 1; 35 (7): 2230-8.

AbstractRecombination-activating gene (RAG)1 and RAG2 encode T and B lymphocyte-specific endonucleases indispensable for rearrangements of antigen-receptor gene segments but also capable of causing deleterious chromosome rearrangements. The mechanisms regulating RAG expression and repression are not clear. Here we identify NWC, a third evolutionarily conserved gene within the RAG locus, and show that it is ubiquitously expressed, with the notable exception of RAG-nonexpressing immature and mature T and B lymphocytes because in lymphocytes it is regulated by the RAG1 promoter and transcribed as RAG1-NWC hybrid mRNA molecules. We also show that in all other cells NWC is controlled by the RAG2 intragenic promoter, which in immature and mature T and B lymphocytes is silent. The possible implications of these findings for understanding the activation and inactivation of RAG genes in lymphocytes and their repression in other cells are discussed.

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