Regulation of interferon gene expression: mechanism of action of the If-1 locus.

We have examined the mechanism of action of the If-1 interferon (IFN) regulatory locus. This locus controls the level of circulating IFN produced in inbred mice in response to intravenous injection of Newcastle disease virus. Mice carrying the If-1h (high) allele show circulating IFN levels 10- to 15-fold higher than those carrying the If-1l (low) allele. In this report we show that induced splenocytes from If-1h and If-1l mice produce IFN at levels which are in the same proportions as those found in the circulation. Higher levels of IFN-specific mRNA were observed in splenocyte populations from If-1h animals. This was due to increased transcription of IFN genes. At the same time, the high- and low-producing populations showed no significant difference in the number of IFN mRNA-containing cells. We conclude that the effect of If-1 in the spleen is to control the levels of transcription of the IFN genes in individual induced splenocytes.