The mechanism of expansion of late erythroid progenitors during erythroid regeneration: target cells and effects of erythropoietin and interleukin-3

Through immunologic means we have been able to separate primate bone marrow cells into populations containing late erythroid progenitors (colony forming units [CFUe] and e-clusters) but depleted of early erythroid progenitors (burst-forming units [BFUe]) or populations enriched in BFUe in relation to late progenitors. We used these fractionated populations in a two stage liquid/semisolid culture system and have assessed the effect of erythropoietin (Epo) and interleukin-3 (IL-3) on the proliferation and differentiation of erythroid progenitors in the presence or absence of early progenitors. We found that populations that contained CFUe but were depleted of BFUe failed to show any amplification of CFUe or e-clusters in the presence of Epo (or Epo plus IL-3). In contrast, populations containing BFUe yielded a striking (sixfold for CFUe; 23-fold for e-clusters) expansion of late progenitors in the presence of Epo. Maximum amplification (15-fold for CFUe; 32-fold for e-clusters) was achieved when both IL-3 and Epo were present in culture. Our results imply that CFUe and e-clusters lack the capacity to amplify their numbers and suggests that the expansion of late erythroid progenitors during rapid erythroid regeneration is accomplished by influx of BFUe rather than amplification of CFUe. These data are of relevance to models of acute marrow expansion and to the mechanism of activation of fetal hemoglobin production during rapid erythroid regeneration.