Article abstract
Nature Immunology 9, 203 - 215 (2008)
Published online: 6 January 2008 | doi:10.1038/ni1555
Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5
Jagan M R Pongubala1,5, Daniel L Northrup2,5, David W Lancki1, Kay L Medina1,4, Thomas Treiber3, Eric Bertolino1, Matthew Thomas2, Rudolf Grosschedl3, David Allman2 & Harinder Singh1
Abstract
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/EBP
, 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.
- Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA.
- Department of Pathology and Laboratory of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
- Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology, Freiburg 79108, Germany.
- Present address: Department of Immunology, The Mayo Clinic, Rochester, Minnesota 55905, USA.
- These authors contributed equally to this work.
Correspondence to: Harinder Singh1 e-mail: hsingh@uchicago.edu
Correspondence to: David Allman2 e-mail: dallman@mail.med.upenn.edu
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