Immunological studies of aging. II. Loss of IgG and high avidity plaque-forming cells and increased suppressor cell activity in aging mice.

Abstract

The magnitude and heterogeneity of the immune response to dinitrophenylated bovine gamma globulin was measured in aged and young mice at a cellular level using an inhibition of plaque-forming cell assay. The primary and secondary responses of 24-mo-old mice were markedly depressed in magnitude and restricted in avidity for the DNP determinant when compared to 2-mo-old animals. Bacterial lipopolysaccharide given at the time of immunization increased the restriction in heterogeneity seen in 12- and 24-mo-old mice. Indirect PFCs were more severely depressed than direct PFCs in 24-mo-old mice. Syngeneic, lethally irradiated, 2-mo-old mice reconstituted with aged spleen cells exhibit the depressed and restricted response to DNP-BGG seen in old mice. When 10(8) young thymus cells were given together with old spleen cells the heterogeneity of the response was increased. When 2-mo- and 24-mo-old spleen cells were transferred together into young recipients the magnitude of the response to the young spleen cells markedly reduced. Thus, there appears to be a loss of thymic-helper cells and an increase in suppressor activity in aged animals.

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.…”

Repertoire of Antibody Response in Bone Marrow and the Memory Response Are Differentially Affected in Aging Mice

“…The aged immune system tends to generate Abs with lower avidity and/or affinity compared with young controls (3)(4)(5)(6)(7). Thus, even if the response of am aged organism to a specific Ag remains vigorous, the Abs are functionally insufficient and fail to protect against infection (8 -10).…”

B cells from aged mice exhibit reduced apoptosis upon B-cell antigen receptor stimulation and differential ability to up-regulate survival signals

“…Specifically, B cell function declines with age and this age-related changes in the B cell compartment has been associated with alteration in T cell-help and also with intrinsic B cell defects [2]. Humoral response disturbances include the production of a greater proportion of lowaffinity antibodies [6,7], different VH gene usage [8] and incidence of autoreactive antibodies [9,10].…”