B cell memory but not antibody response is maintained in the elderly after repeated influenza vaccine immunizations and aged murine plasma cell generation is defective (VAC11P.1066)

Abstract

Abstract The success of a vaccine depends on both plasma cells and memory B cells. We previously showed that serum antibodies and the in vitro AID response to a new influenza vaccine are decreased in elderly individuals. We hypothesized that even though AID is decreased in the elderly, the ability to generate memory B cells might be improved by a repeated vaccine. To test this hypothesis, we recruited young and elderly individuals who had been immunized in at least two consecutive influenza vaccine seasons in which the H1N1 strain was the same. Results showed that frequencies of influenza vaccine-specific memory B cells were similar in young and elderly individuals but the levels of serum antibodies were lower in the elderly. These findings suggest that multiple re-exposures to the vaccine cause a divergence between memory B cell frequencies and antibody levels with age, which could be due to impaired memory B cell to plasma cell differentiation in the elderly. To test the hypothesis of defective plasma cell development in old mice, we measured the percentage of plasma cells and Blimp-1 in LPS-stimulated B cells and found them significantly lower in old than in young cultures. The average fold reduction in the secreted amount of IgM and IgG3 in aged cultures compared to young cultures is higher than the average reduction in CD138+ plasma cells (10-fold vs 2-fold) suggesting qualitative as well as quantitative plasma cell defects with age.