Concurrent or sequential delta and beta TCR gene rearrangement during thymocyte development: individual thymi follow distinct pathways.
Analysis of TCR rearrangement profiles of well-defined thymocyte populations in a number of individual thymi provides evidence for a new pathway of lineage commitment. In all of the thymi analyzed, alphabeta thymocytes have rearrangements in the delta locus that are enhanced for out-of-frame rearrangements. Thus, not only did alphabeta thymocytes pass through a stage in differentiation that included delta rearrangement, but they also constitute a population that was relatively unsuccessful at these rearrangements. Interestingly, in some thymi, gammadelta thymocytes have out-of-frame beta rearrangements. This represents a novel pathway in which delta and beta rearrangement happens concurrently. In this pathway, selection favors whichever gene is in frame, thus improving the chances of generating useful T cells. In other thymi, gammadelta cells showed no obvious beta gene rearrangement, indicating a sequential rearrangement. Thus, alphabeta/gammadelta lineage commitment can follow at least two distinct pathways in different individuals.
Margolis
D
D
Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee 53226, USA. dam@post.its.mcw.edu
Yassai
M
M
Hletko
A
A
McOlash
L
L
Gorski
J
J
D002454:Cell Differentiation; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta