Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Nat Immunol. 2013 Aug;14(8):867-75. doi: 10.1038/ni.2641. Epub 2013 Jun 30.
The transcription factors EBF1 and Pax5 have been linked to activation of the B cell lineage program and irreversible loss of alternative lineage potential (commitment), respectively. Here we conditionally deleted Ebf1 in committed pro-B cells after transfer into alymphoid mice. We found that those cells converted into innate lymphoid cells (ILCs) and T cells with variable-diversity-joining (VDJ) rearrangements of loci encoding both B cell and T cell antigen receptors. As intermediates in lineage conversion, Ebf1-deficient CD19(+) cells expressing Pax5 and transcriptional regulators of the ILC and T cell fates were detectable. In particular, genes encoding the transcription factors Id2 and TCF-1 were bound and repressed by EBF1. Thus, both EBF1 and Pax5 are required for B lineage commitment by repressing distinct and common determinants of alternative cell fates.
转录因子 EBF1 和 Pax5 分别与 B 细胞谱系程序的激活和替代谱系潜能的不可逆丧失(定向分化)有关。在这里,我们在将细胞转移到无淋巴小鼠后,条件性地删除了已定向的前 B 细胞中的 Ebf1。我们发现这些细胞转变成了先天淋巴细胞(ILC)和 T 细胞,并且这些细胞中编码 B 细胞和 T 细胞抗原受体的基因座发生了可变多样性连接(VDJ)重排。作为谱系转换的中间产物,可以检测到 Ebf1 缺陷的 CD19(+)细胞表达 Pax5 和 ILC 和 T 细胞命运的转录调节因子。特别是,编码转录因子 Id2 和 TCF-1 的基因被 EBF1 结合并抑制。因此,EBF1 和 Pax5 都通过抑制替代细胞命运的不同和共同决定因素来共同促进 B 细胞谱系的定向分化。