University of California San Diego, Division of Biology, La Jolla, California, USA.
Nat Immunol. 2010 Mar;11(3):240-9. doi: 10.1038/ni.1845. Epub 2010 Feb 14.
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.
E 蛋白是碱性螺旋-环-螺旋转录因子，调节淋巴细胞发育的许多关键方面。胸腺细胞表达多种 E 蛋白，这些蛋白被认为提供了对于 T 细胞分化至关重要的协同和补偿功能。与这一观点相反，我们在此报告，E 蛋白 HEB 在 T 细胞发育的 CD4(+)CD8(+)双阳性 (DP) 阶段是唯一需要的。缺乏 HEB 的胸腺细胞表现出存活受损、无法对编码 T 细胞抗原受体 α 链 (Tcra) 的基因中的可变-α (V(alpha)) 片段进行远侧连接-α (J(alpha)) 片段的重排，并且在其最早的祖细胞阶段固有地严重阻断了不变自然杀伤 T 细胞 (iNKT 细胞) 的发育。因此，我们的结果表明，HEB 是 T 细胞发育和 iNKT 细胞谱系产生中的特定和必需因子，定义了 HEB 在调节淋巴细胞成熟中的独特作用。
