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E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression.

Publication ,  Journal Article
Wojciechowski, J; Lai, A; Kondo, M; Zhuang, Y
Published in: J Immunol
May 1, 2007

Thymocytes undergoing TCRbeta gene rearrangements are maintained in a low or nonproliferating state during early T cell development. This block in cell cycle progression is not released until the expression of a functional pre-TCR, which is composed of a successfully rearranged TCRbeta-chain and the Pre-Talpha-chain. The regulatory molecules responsible for the coordination of these differentiation and proliferation events are currently unknown. E2A and HEB are structurally and functionally related basic helix-loop-helix transcription factors involved in T cell development. To reveal the function of E2A and HEB through the stage of pre-TCR expression and alleviate functional compensation between E2A and HEB, we use a double-conditional knockout model. The simultaneous deletion of E2A and HEB in developing thymocytes leads to a severe developmental block before pre-TCR expression and a dramatic reduction of Pre-Talpha expression. These developmentally arrested thymocytes exhibit increased proliferation in vivo and dramatic expansion ex vivo in response to IL-7 signaling. These results suggest that E2A and HEB are not only critical for T cell differentiation but also necessary to retain developing thymocytes in cell cycle arrest before pre-TCR expression.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 1, 2007

Volume

178

Issue

9

Start / End Page

5717 / 5726

Location

United States

Related Subject Headings

  • Transcription Factor 7-Like 1 Protein
  • TCF Transcription Factors
  • T-Lymphocytes
  • Sequence Deletion
  • Receptors, Antigen, T-Cell, alpha-beta
  • Mice, Knockout
  • Mice
  • Lymphocyte Count
  • Lymphocyte Activation
  • Interleukin-7
 

Citation

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Wojciechowski, J., Lai, A., Kondo, M., & Zhuang, Y. (2007). E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression. J Immunol, 178(9), 5717–5726. https://doi.org/10.4049/jimmunol.178.9.5717
Wojciechowski, Jason, Anne Lai, Motonari Kondo, and Yuan Zhuang. “E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression.J Immunol 178, no. 9 (May 1, 2007): 5717–26. https://doi.org/10.4049/jimmunol.178.9.5717.
Wojciechowski J, Lai A, Kondo M, Zhuang Y. E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression. J Immunol. 2007 May 1;178(9):5717–26.
Wojciechowski, Jason, et al. “E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression.J Immunol, vol. 178, no. 9, May 2007, pp. 5717–26. Pubmed, doi:10.4049/jimmunol.178.9.5717.
Wojciechowski J, Lai A, Kondo M, Zhuang Y. E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression. J Immunol. 2007 May 1;178(9):5717–5726.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 1, 2007

Volume

178

Issue

9

Start / End Page

5717 / 5726

Location

United States

Related Subject Headings

  • Transcription Factor 7-Like 1 Protein
  • TCF Transcription Factors
  • T-Lymphocytes
  • Sequence Deletion
  • Receptors, Antigen, T-Cell, alpha-beta
  • Mice, Knockout
  • Mice
  • Lymphocyte Count
  • Lymphocyte Activation
  • Interleukin-7