The antiproliferative effect of murine interferon alpha/beta on early bone marrow-derived erythroid precursors...

We have examined the antiproliferative effect of murine interferon (MuIFN) alpha/beta on a primitive class of erythroid precursors, the burst-forming units (BFUe) which give rise to macroscopic colonies of erythroblasts in plasma clots. Cultures were examined respectively on day 9 and on day 15; in both instances there was a significant reduction in the number of erythropoietic bursts in cultures exposed to IFN. The effect of IFN was more pronounced when the cells were cultured in the presence of suboptimal concentrations of erythropoietin and it could to a significant extent be reversed by ouabain at 10(-15) M. The latter finding is in line with observations made by others that growth factors can act as IFN antagonists. A comparison of BFUe derived from mice of two different genotypes, BALB/c and C57BL/6, revealed no difference in relative sensitivity to the antiproliferative effect of IFN. This is in contrast with the previously described fivefold greater sensitivity of the BALB/c genotype when a more differentiated class of erythroid precursors, the colony-forming units or CFUe, are exposed to IFN. Since the BFUe, studied in the present work, are a more primitive class of erythroid precursors than the CFUe, it can be concluded that the genes modulating the difference in sensitivity to IFN action on erythroid precursors are only expressed after a certain stage of differentiation has been reached.