Enforced expression of EBF in hematopoietic stem cells restricts lymphopoiesis to the B cell lineage.
Mice deficient in early B cell factor (EBF) are blocked at the progenitor B cell stage prior to immunoglobulin gene rearrangement. The EBF-dependent block in B cell development occurs near the onset of B-lineage commitment, which raises the possibility that EBF may act instructively to specify the B cell fate from uncommitted, multipotential progenitor cells. To test this hypothesis, we transduced enriched hematopoietic progenitor cells with a retroviral vector that coexpressed EBF and the green fluorescent protein (GFP). Mice reconstituted with EBF-expressing cells showed a near complete absence of T lymphocytes. Spleen and peripheral blood samples were >95 and 90% GFP+EBF+ mature B cells, respectively. Both NK and lymphoid-derived dendritic cells were also significantly reduced compared with control-transplanted mice. These data suggest that EBF can restrict lymphopoiesis to the B cell lineage by blocking development of other lymphoid-derived cell pathways.
Zhang
Zheng
Z
Department of Microbiology, Division of Developmental and Clinical Immunology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Cotta
Claudiu V
CV
Stephan
Robert P
RP
deGuzman
Cristina G
CG
Klug
Christopher A
CA
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D008164:Luminescent Proteins / Q000235:genetics; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; D008164:Luminescent Proteins; D015534:Trans-Activators; D049452:Green Fluorescent Proteins