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Terminal deoxynucleotidyl transferase and repertoire development
C L Benedict1, S Gilfillan, T H Thai
1Princeton University, Department of Molecular Biology, New Jersey, USA.
Immunological Reviews
|August 10, 2000
Summary
Terminal deoxynucleotidyl transferase (Tdt) is crucial for lymphocyte development. Its absence promotes protective fetal-like immune cells, while premature activity impairs antibody production.
Area of Science:
- Immunology
- Molecular Biology
- Developmental Biology
Background:
- Terminal deoxynucleotidyl transferase (Tdt) plays a role in V(D)J recombination.
- Tdt activity influences lymphocyte repertoire development.
- The precise regulatory mechanisms of Tdt splice forms are under investigation.
Purpose of the Study:
- To investigate the impact of Tdt absence and premature activity on lymphocyte development and immune function in mice.
- To explore the role of Tdt in generating protective immune responses.
- To understand how Tdt influences the T and B-cell repertoire.
Main Methods:
- Gene-targeted disruption of Tdt in mice.
- Analysis of lymphocyte development and immune cell populations.
- Assessment of antibody production and repertoire diversity.
Main Results:
- Absence of Tdt during development generates fetal-like lymphocyte clones with protective immunity.
- Premature Tdt activity impairs the development of these protective clones and antibody production.
- Tdt gene disruption promotes the development of fetal-like T and B-cell clones into adulthood, altering the repertoire.
Conclusions:
- Tdt is a key regulator of V(D)J recombination and lymphocyte repertoire development.
- Modulating Tdt activity can influence the generation of protective immune responses.
- Alternative splice forms of Tdt may provide regulatory mechanisms for N addition during lymphocyte development.