Hematopoetic precursors respond to a unique B lymphocyte-derived factor in vivo.
In this study we detected a factor that stimulates the proliferation of bone marrow-derived hematopoietic precursors in diffusion chambers implanted in mice. This factor, called diffusible colony-stimulating factor (D-CSF), was found in medium conditioned in the presence of spleen and peripheral blood cells from mice with B cell leukemia (BCL1). After the administration of D-CSF, the number of colonies formed in the plasma clot inside the chamber (CFU-DG) was increased, as were the number of hematopoietic precursors (CFU-MIX, CFU-S, CFU-C, and BFU-E) as judged by a subculture of diffusion chamber contents. Depletion of macrophages and T cells from the spleen cell suspension did not decrease the production of D-CSF, thereby indicating that it was derived from B cells. Neoplastic BCL1 cells appear to be the source because D-CSF could not be detected in medium conditioned with normal B cells. BCL1-conditioned medium (CM) did not enhance CFU-MIX, BFU-E, and CFU-C colony formation in vitro, which suggested that D-CSF is different from multi-CSF, EPA, or CSF. The addition of BCL1 CM to multi-CSF-, erythroid potentiating activity (EPA), and CSF (EL-4CM)-containing cultures had no effect on CFU-MIX, BFU-E, and CFU-C colony formation, thus indicating the absence of a synergistic or inhibitory activity. On the other hand, EL-4 CM, which stimulates CFU-MIX, BFU-E, and CFU-C in vitro, had no effect on CFU-DG in vivo. Biochemical characterization of BCL1 CM revealed that D-CSF is relatively heat stable and loses its bioactivity with protease treatments. It binds to lentil-lectin, according to gel-filtration chromatography has a relative molecular weight of approximately 43,000, and on reverse-phase high-performance liquid chromatography elutes with acetonitrile. These data also indicate that transformed B cells may serve as a source for hematopoietic regulators that act on hematopoietic precursors in vivo.
Niskanen
E
E
Department of Internal Medicine, University of Virginia, School of Medicine, Charlottesville 22908.
Gorman
J
J
Isakson
P C
PC
D000324:Adrenocorticotropic Hormone / Q000032:analysis; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006410:Hematopoiesis; D016298:Hematopoietic Cell Growth Factors; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008970:Molecular Weight; D014407:Tumor Cells, Cultured / Q000502:physiology*
D003115:Colony-Stimulating Factors; D006023:Glycoproteins; D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D008222:Lymphokines; D000324:Adrenocorticotropic Hormone