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Clonal proliferation unlinked to terminal deoxynucleotidyl transferase synthesis in thymocytes of young mice

Rothenberg, Ellen and Triglia, Dennis (1983) Clonal proliferation unlinked to terminal deoxynucleotidyl transferase synthesis in thymocytes of young mice. Journal of Immunology, 130 (4). pp. 1627-1633. ISSN 0022-1767. https://resolver.caltech.edu/CaltechAUTHORS:20170213-091823076

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Abstract

Terminal deoxynucleotidyl transferase (TdT) is a specialized DNA polymerase that is potentially mutagenic. It is expressed only in the thymus and in some bone marrow cells, suggesting that it acts selectively in immature lymphoid cells, especially T cells. We investigated the extent to which de novo synthesis of TdT is correlated with the clonal expansion that T cell precursors undergo in the thymus. Using biosynthetic pulse-labeling and immune precipitation, we found that thymocytes from late-fetal and neonatal mice make TdT at considerably lower levels than weanling or adult mouse thymocytes. Adult levels of TdT synthesis are only reached a week after birth. Thus, the high proportion of proliferating cells in the perinatal thymus does not entail a correspondingly high production' of TdT synthesis is blocked by cytolytic treatment with anti-Lyt-2 and complement, suggesting that the inducible cells are already Lyt-2+ like most adult TdT+ thymocytes. These observations imply that the stroma of the perinatal thymus either suppresses or fails to trigger high-level TdT synthesis. At the same time, it is in this microenvironment that maximum proliferation and export of functional T cell precursors take place. In contrast, the conditions that stimulate high TdT synthesis in vitro are not associated with mitogenesis but rather with growth arrest. High-level TdT synthesis in general is not regulated so as to precede or coincide with clonal expansion, either in perinatal or in adult thymocyte populations. The possibility remains that in many cells it is linked with a commitment to die.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.jimmunol.org/content/130/4/1627PublisherArticle
ORCID:
AuthorORCID
Rothenberg, Ellen0000-0002-3901-347X
Additional Information:© 1983 American Association of Immunologists. Received for publication October 18, 1982. Accepted for publication December 23, 1982. This work was supported by National Institutes of Health Grants AI 16769, CA 31667, and AI 19752. We thank David Baltimore, Ulrich Hammerling, Robert Hyman, Allen Silverstone, and Owen Witte for donating the immunologic reagents that made these studies possible. We are also very grateful to Eric Davidson, Lee Hood and Howard Jacobs for their thoughtful and incisive criticism of the manuscript.
Funders:
Funding AgencyGrant Number
NIHAI16769
NIHCA31667
NIHAI19752
Issue or Number:4
Record Number:CaltechAUTHORS:20170213-091823076
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170213-091823076
Official Citation:Clonal proliferation unlinked to terminal deoxynucleotidyl transferase synthesis in thymocytes of young mice. E Rothenberg, D Triglia The Journal of Immunology April 1, 1983, 130 (4) 1627-1633
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74228
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:13 Feb 2017 20:10
Last Modified:03 Oct 2019 16:36

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