Peripheral B cells in old mice have extended survival. (A-B) Splenic B cells from young, old, or old hCD20Tg mice treated for B-cell depletion that have reconstituted their peripheral B-cell compartment from de novo B-cell lymphopoiesis in the BM (old depleted) were cultured for the indicated time intervals. Cells were collected and fixed, and spontaneous death was determined by propidium iodide (PI) staining. Shown are representative results after 24 hours (A) and kinetic measurements of accumulated spontaneous apoptosis (B). Significance of differences between groups of young and old mice or between old-depleted mice and old mice are marked with stars (n = 6 mice from each group in a total of 4 independent experiments). (C-D) Young and old Mx-cre/RAG-2^fl/fl or control mice were injected intraperitoneally with polyinosinic:polycytidylic acid [poly(I:C)] to ablate floxed alleles, and 17 weeks later, spleens were analyzed to quantify B cells. Shown are representative plots for individual mice with the indicated genotypes (C) and absolute cell numbers (D). Graph depicts means from 5 mice in each group ± standard error (SE). **P < .01; ***P < .001.