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Nat Immunol. 2010 Mar;11(3):240-9. doi: 10.1038/ni.1845. Epub 2010 Feb 14.

An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells.

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University of California San Diego, Division of Biology, La Jolla, California, USA.

Erratum in

  • Nat Immunol. 2010 Jul;11(7):644.


E proteins are basic helix-loop-helix transcription factors that regulate many key aspects of lymphocyte development. Thymocytes express multiple E proteins that are thought to provide cooperative and compensatory functions crucial for T cell differentiation. Contrary to that, we report here that the E protein HEB was uniquely required at the CD4(+)CD8(+) double-positive (DP) stage of T cell development. Thymocytes lacking HEB showed impaired survival, failed to make rearrangements of variable-alpha (V(alpha)) segments to distal joining-alpha (J(alpha)) segments in the gene encoding the T cell antigen receptor alpha-chain (Tcra) and had a profound, intrinsic block in the development of invariant natural killer T cells (iNKT cells) at their earliest progenitor stage. Thus, our results show that HEB is a specific and essential factor in T cell development and in the generation of the iNKT cell lineage, defining a unique role for HEB in the regulation of lymphocyte maturation.

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