Terminal deoxynucleotidyl transferase and repertoire development.
In mice, the absence of terminal deoxynucleotidyl transferase (Tdt) expression during fetal and neonatal life provides a window in development where clones of lymphocytes are generated that provide protective immunity. Introducing premature Tdt activity interferes with the development of these clones and results in an impaired ability to make protective antibodies. Conversely, 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 repertoire. The alternative splice forms of Tdt may be necessary to provide regulatory mechanisms to restrict N addition to appropriate stages of the developmental pathways, the details of which are being revealed. The evidence continues to build that Tdt is a key player in influencing the outcome of V(D)J recombination during lymphocyte and repertoire development.
Benedict
C L
CL
Princeton University, Department of Molecular Biology, New Jersey, USA.
Gilfillan
S
S
Thai
T H
TH
Kearney
J F
JF
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D004253:DNA Nucleotidylexotransferase / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009711:Nucleotides / Q000378:metabolism; D010767:Phosphorylcholine / Q000276:immunology; D020033:Protein Isoforms; D013601:T-Lymphocytes / Q000276:immunology; D019076:Transgenes
D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D009711:Nucleotides; D020033:Protein Isoforms; D010767:Phosphorylcholine; D004253:DNA Nucleotidylexotransferase