Terminal deoxynucleotidyl transferase and repertoire development

In mice, the absence of terminal deoxynucleotidyl transferase (Tdt) express ion during fetal and neonatal life provides a window in development where c lones of lymphocytes are generated that provide protective immunity. Introd ucing premature Tdt activity interferes with the development of these clone s and results in an impaired ability to make protective antibodies. Convers ely, gene-targeted disruption of Tdt prevents N additions at all stages of T and B-lymphocyte development and promotes the development of Fetal-like T and B-cell clones into adulthood, with accompanying alterations in reperto ire. The alternative splice forms of Tdt may be necessary to provide regula tory mechanisms to restrict N addition to appropriate stages of the develop mental pathways, the details of which are being revealed. The evidence cont inues to build that Tdt is a key player in influencing the outcome of V(D)J recombination during lymphocyte and repertoire development.