Plasma cell numbers decrease in bone marrow of old patients

Abstract

The BM is well understood to play a key role in plasma cell homing and survival in mice. In humans, BM plasma cells and their functions are less well characterized. In this study, we used paired bone biopsies from the femur shaft and blood samples from persons of different ages to analyze age-related changes of plasma and memory B cells. Our results demonstrated that plasma cells were mainly located in the BM, while a higher percentage of memory B cells was in the peripheral blood than in the BM. The frequency of plasma and memory B cells from both sources decreased with age, while immature and naïve B cells were unaffected. An age-related decline of tetanus-and diphtheria-specific BM plasma cells was observed, whereas influenza A-and cytomegalovirus-specific BM plasma cells were not affected. With the exception of cytomegalovirus, peripheral antibody concentrations correlated with BM plasma cells of the same specificity, but were independent of antigen-specific peripheral blood memory B cells. Our results demonstrate that the BM houses decreased numbers of plasma cells in old age. The number of cells of certain specificity may reflect the number and time point of previous antigen encounters and intrinsic age-related changes in the BM. Keywords: Aging r Bone marrow r Memory B cells r Plasma cellsAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionImmunologic memory is a hallmark of the adaptive immune system. Previous studies indicate that the BM is a secondary lymphoid organ and a major reservoir of memory CD4 + and CD8 + T cells + population were significantly decreased in BMMCs in the older age group, whereas the percentages of immature and naïve B cells were similar in both age groups ( Fig. 2A and C). Similar results to BMMCs were observed for PBMCs (Fig. 2B and D). Functional characterization of BM plasma cells and PB memory B cells in old ageNext, we analyzed the impact of aging on the frequency of antigenspecific BM plasma cells, PB-derived memory B cells as well as on peripheral antibody concentrations. Tetanus and diphtheria represent antigens against which most of our donors had been immunized in the past, but for which natural exposure is unlikely. In contrast, influenza A is a pathogen which is encountered frequently by natural exposure and/or vaccination. Cytomegalovirus (CMV) is a persistent virus which during latent infection chronically stimulates immune responses. The frequencies of tetanus-and diphtheria-specific BM plasma cells correlated negatively with age ( Fig. 3A). In contrast, no correlation between influenza A-specific BM plasma cells and age was observed. The frequency of CMV-specific BM plasma cells did not change with age in persons with a positive serotype.To assess age-related alterations of PB-derived memory B cells of a certain specificity, isolated PBMCs were preactivated with pokeweed mitogen, ODN2006, and Staphylococcus aureus Cowan to stimulate antibody production. The percentage of antibodysecreting ce...

Immune System Dysfunction in the Elderly

“…Plasma cell numbers decrease in the bone marrow of old patients (Pritz et al 2015). This reduction of clonal expansion of plasma cells results in a low affinity of antibodies to antigens (Dunn-Walters et al 2003, Effros et al 2005, Johnson and Cambier 2004.…”

Immunological memories of the bone marrow

“…In regenerating tissue of acute inflammation, this may help to get rid of tissue‐resident plasma cells of the acute immune reaction, ie, terminate the peak response. It also may contribute to the age‐dependent decay of humoral memory 49, 50…”

“…It also may contribute to the age-dependent decay of humoral memory. 49,50 Although stromal cells are a key element of the memory plasma cell niche, they are not the only element. Stromal cells do not express BAFF or APRIL themselves, and it is obvious that those ligands of BCMA, the second essential survival signal for memory plasma cells, have to be provided by other cells, which we have termed "accessory" cells of the niche.…”

The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations

“…Influenza vaccination is less effective in elderly as compared to young individuals, in part due to decreased generation of specific serum antibodies [10, 15-19], switched memory B cells [10, 16, 20-22], and long-lived PC [13, 23]. Moreover, antibody titers generated in response to a booster vaccination depend on B cell stimulation, differentiation to B memory cells generated during the primary response, and stimulation and differentiation of these to make new plasmablasts and PC [24].…”