Cell cycle kinetics model of LPS-stimulated spleen cells correlates switch region rearrangements with S phase.

The cell cycle kinetics of lipopolysaccharide (LPS)-stimulated spleen cells were measured by acridine orange (AO) staining and flow cytometry. We have devised a computer model to predict the proportions of cells in each cell cycle phase using iteratively varied parameters. The optimum fit between the predicted and observed proportions of cells in various phases of the cell cycle was determined using the minimum sigma chi 2. The model then correlates the variability of intermitotic phase time with the proportion of genomic DNA available for immunoglobulin (Ig) switch region (S mu) rearrangement. This analysis predicts that rearrangements at S mu are cell cycle-dependent events which occur during the first S phase after LPS activation. Molecular analysis of this system confirms these predictions.