flk2/flt3 ligand is a potent cofactor for the growth of primitive B cell progenitors.
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.
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
B E
BE
Hunte
S
S
Hudak
D
D
Campbell
Y
Y
Xu
D
D
Rennick
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D015703:Antigens, CD / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000166:cytology*; D001854:Bone Marrow Cells; D051927:CD24 Antigen; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000032:analysis; D051917:Leukosialin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology; D019089:Stem Cell Factor / Q000494:pharmacology; D051941:fms-Like Tyrosine Kinase 3
D015703:Antigens, CD; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D015851:Interleukin-7; D051917:Leukosialin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D019089:Stem Cell Factor; C084881:flt3 ligand protein; C497971:Flt3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3; D017493:Leukocyte Common Antigens