Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5

Jagan M.R. Pongubala, Daniel L. Northrup, David W. Lancki, Kay L. Medina, Thomas Treiber, Eric Bertolino, Matthew Thomas, Rudolf Grosschedl, David Allman, Harinder Singh

Research output: Contribution to journalArticle

176 Scopus citations

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/EBPα, 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.

Original languageEnglish (US)
Pages (from-to)203-215
Number of pages13
JournalNature immunology
Volume9
Issue number2
DOIs
StatePublished - Feb 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Pongubala, J. M. R., Northrup, D. L., Lancki, D. W., Medina, K. L., Treiber, T., Bertolino, E., Thomas, M., Grosschedl, R., Allman, D., & Singh, H. (2008). Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. Nature immunology, 9(2), 203-215. https://doi.org/10.1038/ni1555