Distinct and opposite diversifying activities of terminal transferase splice variants

Nat Immunol. 2002 May;3(5):457-62. doi: 10.1038/ni788. Epub 2002 Apr 8.


The short splice variant of mouse terminal deoxynucleotidyl transferase (TdTS) catalyzes the addition of nontemplated nucleotides (N addition) at the coding joins of B cell and T cell antigen receptor genes. However, the activity and function of the long isoform of TdT (TdTL) have not been determined. We show here, in vitro and in vivo, that TdTL is a 3'-->5' exonuclease that catalyzes the deletion of nucleotides at coding joins. These findings suggest that the two TdT isoforms may act in concert to preserve the integrity of the variable region of antigen receptors while generating diversity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / immunology*
  • Amino Acid Motifs / immunology
  • Amino Acid Sequence
  • Animals
  • Antigenic Variation / immunology*
  • B-Lymphocytes / enzymology*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / chemistry
  • DNA Nucleotidylexotransferase / genetics
  • DNA Nucleotidylexotransferase / immunology*
  • Isoenzymes / genetics
  • Isoenzymes / immunology
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • RNA / chemistry
  • RNA / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid


  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Isoenzymes
  • RNA
  • DNA Nucleotidylexotransferase

Associated data

  • GENBANK/A23595
  • GENBANK/AF316014
  • GENBANK/P03007