Enhanced Differentiation of Splenic Plasma Cells but Diminished Long-Lived High-Affinity Bone Marrow Plasma Cells in Aged Mice

Abstract

In the present work, we have dissected the mechanisms responsible for the impaired humoral responses in aging. We found that there was a substantially higher level of Ab-forming cells in the spleens of aged mice than that of young controls. However, the number of high-affinity, class-switched Ab-forming cells was severely decreased in the spleen of aged mice. The accumulation of low-affinity IgM Ab-forming cells in the spleens of aged animals was not due to a deficiency in isotype switching because the number of total IgG1 splenic plasma cells was not significantly reduced. Remarkably, plasma cells of both low and high affinity were significantly diminished in the bone marrow of aged mice compared with that of young mice. The results from reconstitution experiments showed that aged bone marrow was less supportive for plasma cells derived from young splenic B cells. These findings suggest that humoral immune deficiency in aging results from at least two mechanisms: the inability to generate sufficient numbers of high-affinity Ab-forming cells, which is a result of diminished germinal center reaction, and the defective bone marrow environment that has diminished ability to support the selection and survival of long-term Ab-forming cells.

Ageing adversely affects the migration and function of marginal zone B cells

“…These data suggest that in aged individuals the ability to regulate responses to TI antigen may be impaired. Furthermore, the decreased shuttling seen by both follicular and MZ B cells inhibits antigen delivery to the follicle and FDC, and may also contribute towards the impaired T‐cell‐dependent immune responses and germinal centre formation observed with age 40, 41, 42, 43…”

Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF

“…Because the immune response to TD antigens is significantly reduced with aging (Goidl et al, 1976;Kishimoto et al, 1980;Zharhary and Klinman, 1986;Klinman and Kline, 1997;Sanchez et al, 2001;Han et al, 2003), but the immune response to TI antigens is not, as old mice immunized with DNP-Ficoll or with type III pneumococcal polysaccharide (SIII) or LPS make as many plaque-forming cells as young mice (Smith et al, 1976;Weksler et al, 1978), the relative maintenance of B cell responses to BAFF may be involved in the preservation of TI antibody responses in aging.…”

Antibiotic Resistance in Nursing Homes

“…There is a decline in humoral immunity caused by a reduction in the population of antibody producing B-cells along with a smaller immunoglobulin diversity and affinity (Han S & Al, 2003) As age advances, there is a decline in both the production of new naive lymphocytes (Hakim FT & Gress RE, 2007), and the functional competence of memory cell populations, with increased frequency and severity of diseases such as cancer, chronic inflammatory disorders and autoimmunity (Ginaldi L & Al, 2001) .…”