Turning T-cell receptor beta recombination on and off: more questions than answers.

Successful V(D)J recombination at the T-cell receptor beta (Tcrb) locus is critical for early thymocyte development. The locus is subject to a host of regulatory mechanisms that impart a strict developmental order to Tcrb recombination events and that insure that Tcrb recombination occurs in an allelically excluded fashion. Progress has been made in the understanding of the cis-acting control of Tcrb locus chromatin structure and the extent to which such accessibility control can account for the developmental regulation of Tcrb recombination. However, recent studies in our laboratory and elsewhere have made it abundantly clear that accessibility control is only part of the story, and multiple additional mechanisms impact both the developmental activation and inactivation of locus recombination events. Here we evaluate our current understanding of developmental regulation at the Tcrb locus. We highlight the many unresolved issues and we discuss how recent concepts emerging from studies of other antigen receptor loci may (or may not) help to resolve these issues.