Aging and developmental transitions in the B cell lineage

Abstract

One explanation for the deterioration of the humoral immune response in elderly individuals is that B lymphopoiesis declines with increasing age. Recent studies report a dramatic decline in pre-B cell numbers in old mice. Surprisingly, the number of mature B cells does not decline with age. To determine if new B cells are made in aged animals despite the drop in pre-B cells, we used 5′-bromo-2-deoxyuridine labeling to determine the production rate of B cells in the bone marrow and spleen of young and old mice. Because of the great variability in the number of early B lineage cells in old mice, we acquired data on >60 young and 50 old mice throughout these experiments. The transitional and mature B cell compartments in the spleen have slower labeling kinetics in old mice as compared to young. By the end of 4 weeks of labeling, an average of only 15% of the mature B cell compartment consists of newly made cells compared to 30% in young mice. However, in contrast to an earlier report, our results indicate that there is no statistical difference in the rate of production of new immature B cells in the marrow of young and old animals. In total, our results confirm previous work showing that mature B cells in old mice have a slower turnover, but more importantly suggest that the defect in mature B cell turnover is not due to a decline in B lymphopoiesis, but rather an inability of the newly made cells to replenish the peripheral compartments.