Ikaros is absolutely required for pre-B cell differentiation by attenuating IL-7 signals
Open accessAbstract
Pre-B cell receptor (pre-BCR) signaling and migration from IL-7-rich environments cooperate to drive pre-B cell differentiation via transcriptional programs that remain unclear. We show that the Ikaros transcription factor is required for the differentiation of large pre-B to small pre-B cells. Mice deleted for Ikaros in pro/pre-B cells show a complete block of differentiation at the fraction C' stage, and Ikaros-null pre-B cells cannot differentiate upon withdrawal of IL-7 in vitro. Restoration of Ikaros function rescues pre-B cell differentiation in vitro and in vivo and depends on DNA binding. Ikaros is required for the down-regulation of the pre-BCR, Igκ germline transcription, and Ig L chain recombination. Furthermore, Ikaros antagonizes the IL-7-dependent regulation of >3,000 genes, many of which are up- or down-regulated between fractions C' and D. Affected genes include those important for survival, metabolism, B cell signaling, and function, as well as transcriptional regulators like Ebf1, Pax5, and the Foxo1 family. Our data thus identify Ikaros as a central regulator of IL-7 signaling and pre-B cell development.
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Mice lacking IKZF1 have a complete block in B-cell differentiation at the pre-pro-B-cell stage.
“mice lacking IKZF1 have a complete block in B-cell differentiation at the pre-pro-B-cell stage.47”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [47]
BTK is essential for normal B-cell development.
“Finally, BTK is essential for normal B-cell development”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [47]
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Bruton tyrosine kinase degradation as a therapeutic strategy for cancer
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- Authors
- Heizmann, B., Kastner, P., & Chan, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Kastner, Philippe
- Chan, Susan
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2013-12-02
- Volume
- 210
- Issue
- 13
- Pages
- 2823-2832
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC3865471
- OpenAlex
- W2136858141
- Cited by
- 101
- References
- 34
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 18 · 2016: 9 · 2015: 5 · 2014: 12
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-BSV3-018, ANR-11-BSV3-0018)
- Institut National de la Santé et de la Recherche Médicale
- Université de Strasbourg
- Fondation ARC pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- 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
- Ikaros, pre-B cell differentiation, IL-7 signaling, pre-B cell receptor signaling, B cell development, transcriptional regulation, EBF1, PAX5, FOXO1
- MeSH terms
- Animals, B-Lymphocytes, Cell Differentiation, Cell Separation, Flow Cytometry, Immunoglobulin kappa-Chains, Immunoglobulin lambda-Chains, Leukemia, Mutation, Phenotype, Recombination, Genetic, Retroviridae, Transcription, Genetic, Signal Transduction, Down-Regulation, Interleukin-7, Mice, Knockout, VDJ Recombinases, Mice, Ikaros Transcription Factor, Transcriptome
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