Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors.
Nature, 2007/9/27;449(7161):473-7.
Cobaleda C[1], Jochum W, Busslinger M
Affiliations
PMID: 17851532
Impact factor: 69.504
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.
MeSH terms
Animals; B-Lymphocytes; Cell Differentiation; DNA-Binding Proteins; Gene Deletion; Gene Rearrangement, B-Lymphocyte; Immunoglobulins; Lymphoma; Mice; Mice, Inbred C57BL; PAX5 Transcription Factor; Stem Cells; T-Lymphocytes; Thymus Gland
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