Repression of Flt3 by Pax5 is crucial for B-cell lineage commitment
- 15 April 2006
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 20 (8) , 933-938
- https://doi.org/10.1101/gad.1396206
Abstract
Early B-lymphopoiesis requires the growth-factor receptors, IL-7R and Flt3, and the activity of a number of transcription factors. One factor, Pax5, is required for commitment to the B-cell lineage, although the molecular mechanism by which this occurs is unknown. We demonstrate here that an important function of Pax5 is to repress Flt3 transcription in B-cell progenitors, as Pax5-deficient pro-B cells express abundant Flt3 that is rapidly silenced upon the reintroduction of Pax5, whereas enforced expression of Flt3 in wild-type progenitors significantly impairs B-cell development. These findings demonstrate that the repression of Flt3 by Pax5 is essential for normal B-lymphopoiesis.Keywords
This publication has 34 references indexed in Scilit:
- Identification of Flt3+ Lympho-Myeloid Stem Cells Lacking Erythro-Megakaryocytic PotentialCell, 2005
- Transcriptional Control of Early B Cell DevelopmentAnnual Review of Immunology, 2004
- Induction of T cell development and establishment of T cell competence from embryonic stem cells differentiated in vitroNature Immunology, 2004
- The Early Progenitors of Mouse Dendritic Cells and Plasmacytoid Predendritic Cells Are within the Bone Marrow Hemopoietic Precursors Expressing Flt3The Journal of Experimental Medicine, 2003
- Key Role of flt3 Ligand in Regulation of the Common Lymphoid Progenitor but Not in Maintenance of the Hematopoietic Stem Cell PoolImmunity, 2002
- Upregulation of Flt3 Expression within the Bone Marrow Lin−Sca1+c-kit+ Stem Cell Compartment Is Accompanied by Loss of Self-Renewal CapacityImmunity, 2001
- Identification of CD19–B220+c-Kit+Flt3/Flk-2+cells as early B lymphoid precursors before pre-B-I cells in juvenile mouse bone marrowInternational Immunology, 2000
- Dendritic Cell Development in Culture from Thymic Precursor Cells in the Absence of Granulocyte/Macrophage Colony-stimulating FactorThe Journal of Experimental Medicine, 1996
- Flt3 ligand supports the differentiation of early B cell progenitors in the presence of interleukin‐11 and interleukin‐7European Journal of Immunology, 1996
- Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitorsImmunity, 1995