Control of B cell development by Ras-mediated activation of Raf

Cell fate commitment in a variety of lineages requires signals conveyed via p21(ras). To examine the role of p21(ras) in the development of B lymphocytes, we generated transgenic mice expressing a dominant-negative form of Ras in B lymphocyte progenitors, using a novel transcriptional element consisting of the E mu enhancer and the lck proximal promoter. Expression of dominant-negative Ras arrests B cell development at a very early stage, prior to formation of the pre-B cell receptor. Furthermore, an activated form of Raf expressed in the same experimental system could both drive the maturation of normal pro-B cells and rescue development of progenitors expressing dominant-negative Ras. Hence p21(ras) normally regulates early development of B lymphocytes by a mechanism that involves activation of the serine/threonine kinase Raf.