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Evidence That the Long Murine Terminal Deoxynucleotidyltransferase Isoform Plays No Role in the Control of V(D)J Junctional Diversity

Unité de Génétique et Biochimie du Développement, Unité de Recherche Associée Centre National de la Recherche Scientifique 2581, Institut Pasteur, Paris, France

Two TdT isoforms have been found in the mouse. The short isoform is known to add N regions to gene segment junctions during V(D)J recombination, but the role of the long (TdTL) isoform is controversial. We have shown that TdTL, although endowed with terminal transferase activity, is thermally unstable and unable to add N regions in vivo. In this study, we demonstrate that TdTL is devoid of 3'-5' exonuclease activity, and provide an analysis of nucleotide deletion and addition patterns in large series of V(D)J coding joins, arguing against a role of TdTL in the control of junctional diversity in Igs and TCRs.