Abstract
We have investigated the role of flk2/flt3 ligand (FL) in B cell lymphopoiesis. The ability of FL to stimulate the growth of immature B cells was assessed using distinct populations: CD43lowB220+ pre-B cells, CD43+B220+ pro-B cells, and CD43+B220low progenitors. FL failed to affect the growth of the pro-B or pre-B cells whether used alone or in combination with stem cell factor (SCF) or IL-7. In striking contrast, FL was a potent cofactor for the CD43+B220low progenitor cells, interacting with either IL-7 and/or SCF to stimulate their growth. The combination of FL with IL-7 plus SCF stimulated maximum expansion of these cells, albeit, less than that stimulated in stromal cell cultures. When the CD43+B220low progenitors were divided based on expression of heat stable Ag (CD24) into a CD24- and a CD24+ subset, the FL-responsive cells were contained only within the CD24- subset. FL interacted with SCF or with IL-7 to stimulate their growth resulting in a 20- and 50-fold increase in cellularity, respectively. Since the CD24- subset was the most immature of the B cell populations studied, our data suggest that FL costimulates the expansion of very primitive B cell progenitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody Formation / drug effects
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Antigens, CD / analysis
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B-Lymphocyte Subsets / cytology*
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Bone Marrow Cells
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CD24 Antigen
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Drug Synergism
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Female
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Hematopoiesis / drug effects
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Hematopoiesis / physiology*
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / drug effects*
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Immunophenotyping
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Interleukin-7 / pharmacology
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Leukocyte Common Antigens / analysis
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Leukosialin
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Membrane Glycoproteins*
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Membrane Proteins / pharmacology*
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Mice
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Mice, Inbred BALB C
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Proto-Oncogene Proteins / physiology*
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Receptor Protein-Tyrosine Kinases / physiology*
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Recombinant Proteins / pharmacology
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Sialoglycoproteins / analysis
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Signal Transduction / physiology
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Stem Cell Factor / pharmacology
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fms-Like Tyrosine Kinase 3
Substances
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Antigens, CD
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CD24 Antigen
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Cd24a protein, mouse
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Interleukin-7
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Leukosialin
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Membrane Glycoproteins
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Membrane Proteins
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Proto-Oncogene Proteins
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Recombinant Proteins
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Sialoglycoproteins
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Spn protein, mouse
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Stem Cell Factor
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flt3 ligand protein
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Flt3 protein, mouse
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Receptor Protein-Tyrosine Kinases
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fms-Like Tyrosine Kinase 3
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Leukocyte Common Antigens