CONCURRENT OR SEQUENTIAL DELTA-TCR AND BETA-TCR GENE REARRANGEMENT DURING THYMOCYTE DEVELOPMENT - INDIVIDUAL THYMUSES FOLLOW DISTINCT PATHWAYS

Analysis of TCR rearrangement profiles of well-defined thymocyte popul ations in a number of individual thymi provides evidence for a new pat hway of lineage commitment. In all of the thymi analyzed, alpha beta t hymocytes have rearrangements in the delta locus that are enhanced for out-of-frame rearrangements, Thus, not only did alpha beta thymocytes pass through a stage in differentiation that included delta rearrange ment, but they also constitute a population that was relatively unsucc essful at these rearrangements, Interestingly, in some thymi, gamma de lta thymocytes have out-of-frame beta rearrangements, This represents a novel pathway in which delta and beta rearrangement happens concurre ntly, In this pathway, selection favors whichever gene is in frame, th us improving the chances of generating useful T cells, in other thymi, gamma delta cells showed no obvious beta gene rearrangement, indicati ng a sequential rearrangement. Thus, alpha beta/gamma delta lineage co mmitment can follow at least two distinct pathways in different indivi duals.