CONTROL OF B-CELL DEVELOPMENT BY RAS-MEDIATED ACTIVATION OF RAF

Cell fate commitment in a variety of lineages requires signals conveye d via p21(ras). To examine the role of p21(ras) in the development of B lymphocytes, we generated transgenic mice expressing a dominant-nega tive form of Ras in B lymphocyte progenitors, using a novel transcript ional element consisting of the E mu enhancer and the lck proximal pro moter. 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 experiment al system could both drive the maturation of normal pro-B cells and re scue development of progenitors expressing dominant-negative Ras. Henc e p21(ras) normally regulates early development of B lymphocytes by a mechanism that involves activation of the serine/threonine kinase Raf.