Transcription factor ebf1 is essential for the maintenance of b cell identity and prevention of alternative fates in committed cells

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. Access through your institution Buy or

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Sci. USA_ 103, 13789–13794 (2006). CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We thank J.C. Zuniga-Pfucker (University of Toronto) for OP9 and OP9-DL1

cells; J. Kisielow (Eidgenossische Technische Hochschule) for the Beko pre-T cell line; M. Busslinger (Institute of Molecular Pathology, Vienna) for _Pax5_−/− mice; H. Singh (Genentech) for

discussions and advice about the culture of _Ebf1_−/− pre-pro-B cells; I. Falk, S. Fietze and U. Stauffer for help with flow cytometry, genotyping and intravenous injection of mice; A.

Rolink, J. Kirberg and F. Savarese and members of the Grosschedl laboratory for discussions; D. van Essen for critical comments on the manuscript; and M. Rott for help in preparing the

figures and manuscript. Supported by the Max Planck Society (R.G.) and the German Research Foundation (R.G. and A.D.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Cellular

and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany Robert Nechanitzky, Duygu Akbas, Stefanie Scherer, Ildiko Györy, Senthilkumar Ramamoorthy 

& Rudolf Grosschedl * Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany Thomas Hoyler & Andreas Diefenbach Authors * Robert Nechanitzky View

author publications You can also search for this author inPubMed Google Scholar * Duygu Akbas View author publications You can also search for this author inPubMed Google Scholar * Stefanie

Scherer View author publications You can also search for this author inPubMed Google Scholar * Ildiko Györy View author publications You can also search for this author inPubMed Google

Scholar * Thomas Hoyler View author publications You can also search for this author inPubMed Google Scholar * Senthilkumar Ramamoorthy View author publications You can also search for this

author inPubMed Google Scholar * Andreas Diefenbach View author publications You can also search for this author inPubMed Google Scholar * Rudolf Grosschedl View author publications You can

also search for this author inPubMed Google Scholar CONTRIBUTIONS R.N. designed and did experiments, analyzed data and wrote the manuscript; D.A., S.S. and T.H. did experiments and analyzed

data; S.R. did bioinformatic analysis; I.G. provided _Ebf1_fl mice; A.D. supervised research; and R.G. designed and supervised research and wrote the manuscript. CORRESPONDING AUTHOR

Correspondence to Rudolf Grosschedl. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIGURES AND TABLES

Supplementary Figures 1–6 and Supplementary Tables 1 and 2 (PDF 1120 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nechanitzky, R., Akbas, D.,

Scherer, S. _et al._ Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells. _Nat Immunol_ 14, 867–875 (2013).

https://doi.org/10.1038/ni.2641 Download citation * Received: 04 March 2013 * Accepted: 11 May 2013 * Published: 30 June 2013 * Issue Date: August 2013 * DOI: https://doi.org/10.1038/ni.2641

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