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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.
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“Their loss, for example, Pax5 in B cells, can cause plasticity and even cancer6,7,55,56.”
From Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis (2025) · cites this paper as [56]
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Metadata
- Authors
- Nechanitzky, R., Akbas, D., Scherer, S., Györy, I., Hoyler, T., Ramamoorthy, S., Diefenbach, A., & Grosschedl, R.
- Affiliations
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- Max Planck Society (DE)
- University of Freiburg (DE)
- Corresponding author
- Grosschedl, Rudolf
- ORCID
- Venue
- Nature Immunology
- Published
- 2013-06-30
- Volume
- 14
- Issue
- 8
- Pages
- 867-875
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2064993419
- Cited by
- 218
- References
- 50
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 19 · 2023: 12 · 2022: 19 · 2021: 14 · 2020: 19 · 2019: 10 · 2018: 14 · 2017: 17 · 2016: 20 · 2015: 17 · 2014: 18 · 2013: 1
- FWCI
- 10.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- EBF1, B cell identity, lineage commitment, pro-B cells, innate lymphoid cells, T cell fate, PAX5, Id2, TCF1, VDJ rearrangement, conditional gene deletion, transcriptional repression
- MeSH terms
- Animals, B-Lymphocytes, Cell Differentiation, DNA, Gene Expression Regulation, Receptors, Antigen, T-Cell, T-Lymphocytes, Trans-Activators, Polymerase Chain Reaction, Mice, Knockout, Cell Lineage, Adoptive Transfer, Oligonucleotide Array Sequence Analysis, Lymphopoiesis, Mice, V(D)J Recombination
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