• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Early TCR expression and aberrant T cell development in mice with endogenous prerearranged T cell receptor genes.

The factors that regulate the rate of production of T cells by the thymus remain incompletely defined. To test whether generation of functional T cell receptors limits the rate of thymic T cell export, we made use of a line of mice, LN3alphabeta, that have endogenously prerearranged TCR genes. The prerearranged TCR genes were expressed abnormally early in hemopoietic development, indicating that RAG-mediated recombination, rather than transcription factor expression, is the key determinant of the initiation of robust TCR transcription. Thymic T cell export rates were similar between wild-type (wt) and LN3alphabeta mice, indicating that T cell maturation rates in these mice are determined by factors other than TCR gene rearrangement. In competitive bone marrow chimeras, however, LN3alphabeta thymocytes were out-competed by wt cells and failed to develop beyond the double-negative 4 stage. Furthermore, wt progenitors transplanted intrathymically into LN3alphabeta mice proliferated excessively, suggesting that increased proliferative signals in the LN3alphabeta thymus compensate for faulty T cell development driven by early TCR expression.

Pubmed ID: 17617584

Authors

  • Serwold T
  • Hochedlinger K
  • Inlay MA
  • Jaenisch R
  • Weissman IL

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Data

July 15, 2007

Associated Grants

  • Agency: NIAID NIH HHS, Id: 1F 32 AI 58521
  • Agency: NIAID NIH HHS, Id: R01-AI047457
  • Agency: NIAID NIH HHS, Id: R01-AI047458
  • Agency: NCI NIH HHS, Id: R01-CA87869
  • Agency: NICHD NIH HHS, Id: R01-HD0445022
  • Agency: NCI NIH HHS, Id: R37-CA84198
  • Agency: NIAID NIH HHS, Id: T32 AI007290
  • Agency: NCI NIH HHS, Id: T32 CA009151

Mesh Terms

  • Animals
  • Cell Differentiation
  • Flow Cytometry
  • Gene Rearrangement, T-Lymphocyte
  • Genes, RAG-1
  • Mice
  • Mice, Mutant Strains
  • Nuclear Transfer Techniques
  • Receptors, Antigen, T-Cell
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes
  • Thymus Gland