Early activation of TCR alpha gene rearrangement in fetal thymocytes

Abstract

We have previously demonstrated that the onset of TCR α gene rearrangement is mainly restricted to the Jα50 gene in fetal day 16 thymocyte hybridomas. Now, Jα50 rearrangements from fetal thymocyte hybridomas and from day 15.5 fetal thymus have been isolated and sequenced. We demonstrate that Jα50 is rearranged to the rearranged Vδ1Dδ2 gene segment. This indicates that the TCR α rearrangement process is initiated in fetal thymocytes far earlier than previously thought. These thymocytes have their δ genes still accessible for rearrangement and therefore, are controlled by the TCR δ enhancer (Eδ) (and/or another TCR δ specific cis-acting element). Our results further suggest that both Eδ and the TCR α enhancer (Eα) are active at the onset of α rearrangements or alternatively, the initial activation of the Jα locus is controlled by Eδ. In addition, Vδ1Dδ2Jα50 gene segments are replaced by secondary α rearrangements, indicating that thymocytes with the early α rearrangement are committed to the αβ lineage.