Linear differentiation models used to describe the data. Three different models were fitted to the (nonnormalized) DNA 2H-enrichment data. Because fits with a high or low rate of cell division in the BM (pm) are very similar, only the predicted curves with an estimated high pm are shown. The first model (A) assumes simple linear differentiation of CMs to IMs to NCMs in the blood. The other 2 models assume that IMs can mature into NCMs only after a delay of Δ2 days. The second model (B) assumes that this maturation step occurs in the blood, whereas in the third model (C), this takes place outside the circulation. Because the largest differences between the models lay in the fits of the NCMs, predicted curves for NCMs were plotted separately in panel D to allow for easier comparison. The third model produced the best fits (lowest Akaike information criterions), and thus it was used to estimate (E) the residence times of monocytes in the different monocyte subsets, (F) the delays in the PMP and between IM and NCM differentiation, and (G) the percentages of cells that differentiate from CMs into IMs or from IMs into NCMs (supplemental Methods). Data were obtained from 14 individuals, and both data and curves were normalized for plasma enrichment and intracellular dilution of label (supplemental Methods). Individual fits are shown in supplemental Figure 3 and the corresponding parameter estimates in supplemental Tables 1, 2, and 3.
