Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors
Abstract
Lineage commitment and differentiation to a mature cell type are considered to be unidirectional and irreversible processes under physiological conditions. The commitment of haematopoietic progenitors to the B-cell lineage and their development to mature B lymphocytes critically depend on the transcription factor encoded by the paired box gene 5 (Pax5). Here we show that conditional Pax5 deletion in mice allowed mature B cells from peripheral lymphoid organs to dedifferentiate in vivo back to early uncommitted progenitors in the bone marrow, which rescued T lymphopoiesis in the thymus of T-cell-deficient mice. These B-cell-derived T lymphocytes carried not only immunoglobulin heavy- and light-chain gene rearrangements but also participated as functional T cells in immune reactions. Mice lacking Pax5 in mature B cells also developed aggressive lymphomas, which were identified by their gene expression profile as progenitor cell tumours. Hence, the complete loss of Pax5 in late B cells could initiate lymphoma development and uncovered an extraordinary plasticity of mature peripheral B cells despite their advanced differentiation stage.
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Loss of master regulators, such as Pax5 in B cells, can cause plasticity and even cancer.
“Their loss, for example, Pax5 in B cells, can cause plasticity and even cancer6,7,55,56.”
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- Authors
- Cobaleda, C., Jochum, W., & Busslinger, M.
- Affiliations
- Universidad de Salamanca (ES)
- University Hospital Zurich (CH)
- Research Institute of Molecular Pathology (AT)
- Corresponding author
- Busslinger, Meinrad
- Venue
- Nature
- Published
- 2007-09
- Volume
- 449
- Issue
- 7161
- Pages
- 473-477
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1993648538
- Cited by
- 502
- References
- 0
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 22 · 2023: 15 · 2022: 17 · 2021: 15 · 2020: 15 · 2019: 9 · 2018: 21 · 2017: 21 · 2016: 27 · 2015: 30 · 2014: 37 · 2013: 42 · 2012: 35
- FWCI
- 15.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- PAX5, developmental plasticity, lineage reprogramming, T lymphopoiesis, lymphoma, B cell differentiation, transcription factors, immunoglobulin gene rearrangement
- MeSH terms
- Animals, B-Lymphocytes, Cell Differentiation, DNA-Binding Proteins, Immunoglobulins, Lymphoma, Mice, Inbred C57BL, Stem Cells, T-Lymphocytes, Thymus Gland, Gene Rearrangement, B-Lymphocyte, Gene Deletion, Mice, PAX5 Transcription Factor
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