Effect of age on humoral immunity, selection of the B-cell repertoire and B-cell development

The age-associated changes in humoral immunity affect the quality more than the quantity of the antibody response. Changes in the quality of the antibody response with age include shifts in antibody specificities from foreign to autoantigens, in antibody isotypes from IgG to IgM, in antibody affinities from high to low and in the antibody idiotypic repertoire. These changes can be traced to an impaired capacity of T cells to facilitate: (a) the maturation of B cells with respect to isotype and affinity maturation in the periphery and (b) the development of a diverse B-cell repertoire from precursors within the bone marrow. In contrast, there is no evidence that the amount of immunoglobulin produced before or after immunization diminishes with age. Nonetheless, the impaired responses of the elderly to most vaccines and the greater susceptibility of the elderly to infections has fostered a view that immune senescence leads to a state of immune deficiency. However, it is more precise to describe immune senescence as leading to a state of immune dysregulation. The dysregulation of the humoral immunity is manifested by a shift from adaptive humoral immunity, characterized by the production of a highly specific, high-affinity, IgG antibody response to foreign antigens, to a process of natural antibody-mediated immunity, dominated by low-affinity, polyreactive, IgM antibodies which react with autoantigens. Age-associated T-cell impairments appear to be the basis for the shift from adaptive to natural humoral immunity and their reversal should permit the restoration of an adaptive antibody response in the elderly.