title: All-trans- and 9-cis-retinoic acid inhibit growth of normal human and murine B cell precursors.
abstract: In the present paper we demonstrate that physiologic levels (10 nM) of both all-trans- and 9-cis-retinoic acid (RA) are potent inhibitors of the growth of human as well as murine B cell precursors in vitro. Ten nanomolar concentrations of all-trans- and 9-cis-RA reduced the DNA synthesis ([3H]thymidine uptake) of human B cell precursors (CD19+ IgM-) stimulated with O-tetradecanoylphorbol-13-acetate and ionomycin by approximately 55% and 70%, respectively. Human B cell precursors stimulated with low m.w. B cell growth factor were also inhibited by RA. Ten nanomolar concentrations of either isoform of RA reduced DNA synthesis by approximately 50%. No effect of RA on differentiation to sIgM positive cells was noted. The potent growth-inhibiting effect of RA on human B cell precursors was confirmed in the murine cell system. B lymphopoiesis from murine hematopoietic precursors (Lin-B220(+)-containing cells) was induced by stimulation with IL-7. Concentrations of all-trans- and 9-cis-RA as low as 10 pM reduced the colony-forming ability of the IL-7-stimulated Lin-B220(+)-containing cells. Ten nanomolar concentrations of either isoform reduced colony formation by approximately 60%. RA was not toxic to the cells, as the inhibition of colony formation after 24 h was reversible at concentrations as high as 1 microM. The growth-inhibiting effect of RA was directly mediated, as revealed by single cell analysis of the Lin-B220(+)-containing cells. Thus, vitamin A appears to have an important role in regulation of B lymphopoiesis.
authors.affiliation: Department of Immunology, Norwegian Radium Hospital, Montebello, Oslo.
authors.forename: C
authors.initials: C
authors.lastname: Fahlman
authors.forename: S E
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: E B
authors.initials: EB
authors.lastname: Smeland
authors.forename: J
authors.initials: J
authors.lastname: Lømo
authors.forename: C E
authors.initials: CE
authors.lastname: Naess
authors.forename: S
authors.initials: S
authors.lastname: Funderud
authors.forename: H K
authors.initials: HK
authors.lastname: Blomhoff
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D014212:Tretinoin