THE IRG-47 GENE IS IFN-GAMMA INDUCED IN B-CELLS AND ENCODES A PROTEIN WITH GTP-BINDING MOTIFS

The murine pre-B cell line 70Z/3 has been studied extensively as a model system for B cell differentiation induced by cytokines and mitogens. IFN-gamma treatment of 70Z/3 pre-B cells activates IgK L chain gene expression, resulting in the appearance of surface IgM characteristic of B cells. We have isolated and characterized a new cDNA clone, called IRG-47, whose mRNA is transiently elevated up to 30-fold at 4 to 6 h after IFN-gamma induction of 70Z/3 pre-B cells. The IFN-gamma induction of IRG-47 mRNA occurs in all pre-B and in most B lineage cell lines examined but is only induced in three cell lines tested from other lineages. Activation of IRG-47 gene transcription appears to account for the rapid increase in IRG-47 mRNA after induction. Transcription of the IRG-47 gene is down-regulated 10 h postinduction at a time when the level of IRG-47 mRNA is also declining. The complete sequence of the IRG-47 cDNA clone is predicted to encode a 47-KDa protein which, although unique in its sequence, bears resemblance to a number of nucleotide-binding proteins. The IRG-47 coding sequence contains all three highly conserved peptide motifs in the appropriate spacing characteristic of guanine nucleotide-binding proteins.