Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells

被引:148
作者
Nechanitzky, Robert [1 ]
Akbas, Duygu [1 ]
Scherer, Stefanie [1 ]
Gyoery, Ildiko [1 ]
Hoyler, Thomas [2 ]
Ramamoorthy, Senthilkumar [1 ]
Diefenbach, Andreas [2 ]
Grosschedl, Rudolf [1 ]
机构
[1] Max Planck Inst Immunobiol & Epigenet, Dept Cellular & Mol Immunol, Freiburg, Germany
[2] Univ Freiburg, Inst Med Microbiol & Hyg, D-79106 Freiburg, Germany
关键词
LINEAGE SPECIFICATION; GENE-EXPRESSION; T-CELLS; COMMITMENT; PAX5; FOXO1; STEM; DIFFERENTIATION; REARRANGEMENTS; INTERLEUKIN-7;
D O I
10.1038/ni.2641
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:867 / +
页数:10
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