E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression.
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
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
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
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
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