T cell development in TCR beta enhancer-deleted mice: implications for alpha beta T cell lineage commitment and differentiation
Leduc, I.; Hempel, W.M.; Mathieu, N.; Verthuy, C.; Bouvier, G.; Watrin, F.; Ferrier, P.
Journal of Immunology 165(3): 1364-1373
2000
ISSN/ISBN: 0022-1767 PMID: 10903739 Document Number: 520709
T cell differentiation in the mouse thymus is an intricate, highly coordinated process that requires the assembly of T cell receptor (TCR) complexes from individual components, including those produced by the precisely timed V(D)J recombination of TCR genes. Mice carrying a homozygous deletion of the TCR beta transcriptional enhancer (E beta ) demonstrate an inhibition of V(D)J recombination at the targeted TCR beta locus and a block in alpha beta T cell differentiation. In this study, we have characterized the T cell developmental defects resulting from the E beta -/- mutation, in light of previously reported results of the analyses of TCR beta -deficient (TCR beta -/-) mice. Similar to the latter mice, production of TCR beta -chains is abolished in the E beta -/- animals, and under these conditions differentiation into cell-surface TCR-, CD4+CD8+ double positive (DP) thymocytes depends essentially on the cell-autonomous expression of TCR delta -chains and, most likely, TCR gamma -chains. Contrary to previous reports using TCR beta -/- mice, a minor population of TCR gamma delta + DP thymocytes was found within the E beta -/- thymi, which differ in terms of T cell-specific gene expression and V(D)J recombinase activity, from the majority of TCR-, alpha beta lineage-committed DP thymocytes. We discuss these data with respect to the functional role of E beta in driving alpha beta T cell differentiation and the mechanism of alpha beta T lineage commitment.