Molecular Cloning and Characterization of a Novel Stromal Cell-derived CDNA Encoding a Protein That Facilitates Gene Activation of Recombination Activating Gene (RAG)-1 in Human Lymphoid Progenitors

The activation and expression of recombination activation genes (RAGs) in lymphoid progenitors are regulated by signals from surface molecules of stromal cells and/or cytokines. Using a mRNA differential display method, we isolated a novel stromal cell-derived cDNA clone, C2.3, whose transcripts were intensively expressed in RAG-1-inducible stromal cell line, but rarely expressed in RAG-1-non inducible mutant cell line (PA6). The cDNA sequence had no homology to the known genes. The sequence revealed an open reading frame that encodes a 221 amino acid protein with 4 potential transmembrane domains, suggesting a possible role of C2.3 product as a membrane receptor. Introduction of C2.3 cDNA into PA6 mutant line restored the ability to activate RAG-1 gene in lymphoid progenitors, indicating that a C2.3 product may be involved in the induction of RAG-1 gene activation.