| Abstract: |
Development of the αβ and γδ T cell lineages is dependent upon the rearrangement and expression of the TCRα and β or γ and δ genes, respectively. Although the timing and sequence of rearrangements of the TCRα and TCRβ loci in adult murine thymic precursors has been characterized, no similar information is available for the TCRγ and TCRδ loci. In this report, we show that approximately half of the total TCRδ alleles initiate rearrangements at the CD44(high)CD25+ stage, whereas the TCRβ locus is mainly in germline configuration. In the subsequent CD44(low)CD25+ stage, most TCRδ alleles are fully recombined, whereas TCRβ rearrangements are only complete on 10-30% of alleles. These results indicate that rearrangement at the TCRδ locus can precede that of TCRβ locus recombination by one developmental stage. In addition, we find a bias toward productive rearrangements of both TCRδ and TCRγ genes among CD44(high)CD25+ thymocytes, suggesting that functional γδ TCR complexes can be formed before the rearrangement of TCRβ. These data support a model of lineage commitment in which sequential TCR gene rearrangements may influence αβ/γδ lineage decisions. Further, because TCR gene rearrangements are generally limited to T lineage cells, these analyses provide molecular evidence that irreversible commitment to the T lineage can occur as early as the CD44(high)CD25+ stage of development. |
| Keywords: |
nonhuman; polymerase chain reaction; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; gene locus; mice, inbred c57bl; t lymphocyte receptor; gene rearrangement; lymphopoiesis; gene rearrangement, t-lymphocyte; receptors, interleukin-2; antigens, cd44; priority journal; article; gene rearrangement, beta-chain t-cell antigen receptor; gene rearrangement, delta-chain t-cell antigen receptor; gene rearrangement, gamma-chain t-cell antigen receptor
|
