Distinct signals mediate maturation and allelic exclusion in lymphocyte progenitors

Successful in-frame rearrangement of immunoglobulin heavy chain genes or T cell antigen receptor (TCR) beta chain genes in lymphocyte progenitors resu lts in formation of pre-BCR and pre-TCR complexes. These complexes signal p rogenitor cells to mature, expand in cell number, and suppress further rear rangements at the immunoglobulin heavy chain or TCR beta chain loci, thereb y ensuring allelic exclusion. We used transgenic expression of a constituti vely active form of c-Raf-1 (Raf-CAAX) to demonstrate that activation of th e Map kinase pathway can stimulate both maturation and expansion of B and T lymphocytes, even in the absence of pre-TCR or pre-BCR formation. However, the same Raf signal did not mediate allelic exclusion. We conclude that ma turation of lymphocyte progenitors and allelic exclusion require distinct s ignals.