An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells.
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.
University of California San Diego, Division of Biology, La Jolla, California, USA.
Louise M
LM
D'Cruz
Jamie
J
Knell
Jessica K
JK
Fujimoto
Ananda W
AW
Goldrath
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002678:Chimera; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C489532:Tcf12 protein, mouse