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

Nat Immunol. 2013 Aug;14(8):867-75. doi: 10.1038/ni.2641. Epub 2013 Jun 30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cell Lineage
  • DNA / chemistry
  • DNA / genetics
  • Gene Expression Regulation
  • Lymphopoiesis / immunology
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology
  • Trans-Activators / genetics
  • Trans-Activators / immunology*
  • V(D)J Recombination / genetics
  • V(D)J Recombination / immunology

Substances

  • Ebf1 protein, mouse
  • Receptors, Antigen, T-Cell
  • Trans-Activators
  • DNA

Associated data

  • GEO/GSE46349