A novel role for HEB downstream or parallel to the pre-TCR signaling pathway during alpha beta thymopoiesis.

Published

Journal Article

TCR gene rearrangement and expression are central to the development of clonal T lymphocytes. The pre-TCR complex provides the first signal instructing differentiation and proliferation events during the transition from CD4-CD8-TCR- double negative (DN) stage to CD4+CD8+ double positive (DP) stage. How the pre-TCR signal leads to downstream gene expression is not known. HeLa E-box binding protein (HEB), a basic helix-loop-helix transcription factor, is abundantly detected in thymocytes and is thought to regulate E-box sites present in many T cell-specific gene enhancers, including TCR-alpha, TCR-beta, and CD4. Targeted disruption of HEB results in a 5- to 10-fold reduction in thymic cellularity that can be accounted for by a developmental block at the DN to DP stage transition. Specifically, a dramatic increase in the CD4low/-CD8+CD5lowHSA+TCRlow/- immature single positive population and a concomitant decrease in the subsequent DP population are observed. Adoptive transfer test shows that this defect is cell-autonomous and restricted to the alpha beta T cell lineage. Introduction of an alpha beta TCR transgene into the HEBko/ko background is not sufficient to rescue the developmental delay. In vivo CD3 cross-linking analysis of thymocytes indicates that TCR signaling pathway in the HEBko/ko mice appears intact. These findings suggest an essential function of HEB in early T cell development, downstream or parallel to the pre-TCR signaling pathway.

Full Text

Duke Authors

Cited Authors

  • Barndt, R; Dai, MF; Zhuang, Y

Published Date

  • September 15, 1999

Published In

Volume / Issue

  • 163 / 6

Start / End Page

  • 3331 - 3343

PubMed ID

  • 10477603

Pubmed Central ID

  • 10477603

International Standard Serial Number (ISSN)

  • 0022-1767

Language

  • eng

Conference Location

  • United States