Early activation of TCR alpha gene rearrangement in fetal thymocytes

We have previously demonstrated that the onset of TCR alpha gene rearrangem ent is mainly restricted to the J alpha 50 gene in fetal day 16 thymocyte h ybridomas. Now, J alpha 50 rearrangements from fetal thymocyte hybridomas a nd from day 15.5 fetal thymus have been isolated and sequenced. We demonstr ate that J alpha 50 is rearranged to the rearranged V delta 1D delta 2 gene segment. This indicates that the TCR alpha rearrangement process is initia ted in fetal thymocytes far earlier than previously thought. These thymocyt es have their delta genes still accessible for rearrangement and therefore, are controlled by the TCR delta enhancer (E delta) (and/or another TCR del ta specific cis-acting element). Our results further suggest that both E de lta and the TCR alpha enhancer (E alpha) are active at the onset of alpha r earrangements or alternatively, the initial activation of the J alpha locus is controlled by E delta. In addition, V delta 1D delta 2J alpha 50 gene s egments are replaced by secondary alpha rearrangements, indicating that thy mocytes with the early alpha rearrangement are committed to the alpha beta lineage.