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 results in formation of pre-BCR and pre-TCR complexes. These complexes signal progenitor cells to mature, expand in cell number, and suppress further rearrangements at the immunoglobulin heavy chain or TCRbeta chain loci, thereby ensuring allelic exclusion. We used transgenic expression of a constitutively active form of c-Raf-1 (Raf-CAAX) to demonstrate that activation of the 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 maturation of lymphocyte progenitors and allelic exclusion require distinct signals.
Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA. biritani@u.washington.edu
B M
BM
Iritani
J
J
Alberola-Ila
K A
KA
Forbush
R M
RM
Perimutter
D019883:Alkyl and Aryl Transferases / Q000096:biosynthesis / Q000235:genetics; D000483:Alleles; D002454:Cell Differentiation / Q000276:immunology; D004268:DNA-Binding Proteins; D004789:Enzyme Activation / Q000276:immunology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases; D011494:Protein Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C064655:V(D)J recombination activating protein 2; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D011494:Protein Kinases; D019908:Proto-Oncogene Proteins c-raf; D020929:Mitogen-Activated Protein Kinase Kinases