Pongubala Jagan M R, Northrup Daniel L, Lancki David W, Medina Kay L, Treiber Thomas, Bertolino Eric, Thomas Matthew, Grosschedl Rudolf, Allman David, Singh Harinder
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA.
Nat Immunol. 2008 Feb;9(2):203-15. doi: 10.1038/ni1555. Epub 2008 Jan 6.
Alternative lineage restriction and B cell fate commitment require the transcription factor Pax5, but the function of early B cell factor (EBF) in these processes remains mostly unexplored. Here we show that in the absence of EBF, 'expandable' and clonal lymphoid progenitor cells retained considerable myeloid potential. Conversely, ectopic expression of EBF in multipotential progenitor cells directed B cell generation at the expense of myeloid cell fates. EBF induced Pax5 and antagonized expression of genes encoding the transcription factors C/EBPalpha, PU.1 and Id2. Notably, sustained expression of EBF in Pax5-/- hematopoietic progenitor cells was sufficient to block their myeloid and T lineage potential in vivo. Furthermore, in Pax5-/- pro-B cells, higher EBF expression repressed alternative lineage genes. Thus, EBF can restrict alternative lineage 'choice' and promote commitment to the B cell fate independently of Pax5.
替代性谱系限制和B细胞命运决定需要转录因子Pax5，但早期B细胞因子（EBF）在这些过程中的功能大多仍未被探索。我们在此表明，在缺乏EBF的情况下，“可扩增”的克隆性淋巴样祖细胞保留了相当大的髓系潜能。相反，在多能祖细胞中异位表达EBF会以牺牲髓系细胞命运为代价来指导B细胞生成。EBF诱导Pax5表达，并拮抗编码转录因子C/EBPα、PU.1和Id2的基因的表达。值得注意的是，在Pax5-/-造血祖细胞中持续表达EBF足以在体内阻断它们的髓系和T细胞谱系潜能。此外，在Pax5-/-前B细胞中，较高的EBF表达会抑制替代性谱系基因。因此，EBF可以独立于Pax5限制替代性谱系“选择”并促进向B细胞命运的决定。
