A regulatory role of c-Fos in the development of precursor B lymphocytes mediated by interleukin-7.

The proto-oncogene product c-Fos, a component of the transcription factor AP-1, plays a critical role in the expression of genes required for cellular proliferation and differentiation. The c-Fos is induced in early B lineage cells developed in the interleukin-7-dependent bone marrow (BM) cell culture from normal mice. In order to investigate a role of the c-Fos in early B cell development, we have used BM cells from two different transgenic mice carrying the exogenous c-fos gene controlled by the promoter of the H-2Kb gene (H2-c-fos) or the interferon alpha/beta (IFN)-inducible Mx gene (Mx-c-fosD). Development of B lineage cells was retarded in the BM cell culture from H2-c-fos mice. Although B lineage cells normally developed in the BM cell culture from Mx-c-fosD mice without IFN stimulation, the development was completely blocked in the Mx-c-fosD culture when transgenic c-fos was induced in BM cells by IFN stimulation. Furthermore, the IL-7-dependent proliferation of B lineage cells in Mx-c-fosD BM cells was also suppressed by the induction of c-Fos. These results suggest that the c-Fos plays a role as a negative regulator in the early B cell development.