ALL-TRANS-RETINOIC AND 9-CIS-RETINOIC ACID INHIBIT GROWTH OF NORMAL HUMAN AND MURINE B-CELL PRECURSORS

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 s ynthesis ([H-3]thymidine uptake) of human B cell precursors (CD19(+) I gM(-)) stimulated with O-tetradecanoylphorbol-13-acetate and ionomycin by approximately 55% and 70%, respectively. Human B cell precursors s timulated with low m.w. B cell growth factor were also inhibited by RA . Ten nanomolar concentrations of either isoform of RA reduced DNA syn thesis by approximately 50%. No effect of RA on differentiation to slg M 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(+)-cont aining 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 abi lity of the IL-7-stimulated Lin(-)B220(+)-containing cells. Ten nanomo lar concentrations of either isoform reduced colony formation by appro ximately 60%. RA was not toxic to the cells, as the inhibition of colo ny formation after 24 h was reversible at concentrations as high as 1 mu M. The growth-inhibiting effect of RA was directly mediated, as rev ealed by single cell analysis of the Lin(-)B220(+)-containing cells. T hus, vitamin A appears to have an important role in regulation of B ly mphopoiesis.