Restricted onset of T cell receptor alpha gene rearrangement in fetal and neonatal thymocytes.

The initial T cell receptor (TCR) alpha gene rearrangements were analyzed in fetal and neonatal thymocyte hybridomas by Southern blotting. Interestingly, in 30% of all thymocyte hybridomas and in all fetal day 16 thymocyte hybridomas the most proximal J alpha 50 (psi J alpha) gene was rearranged. This rearrangement was found on one chromosome only and mostly in association with a delta rearrangement on the homologous chromosome. J alpha 50 was rearranged to multiple target genes based on the variable size of the restriction fragments. In addition, delta rearrangement was found with a concomitant alpha rearrangement in the majority of hybridomas and it was not only associated with J alpha 50 but with several other rearranged J alpha genes as well. Our results clearly demonstrate that T cell precursors are not pre-committed to either delta or alpha rearrangement but a flexible progenitor responds to multiple regulatory signals during T cell differentiation and they do not support the notion that delta rec-psi J alpha rearrangement is required for cell commitment to TCR alpha gene rearrangement.