Effects of aging on B cell function

Abstract

Summary of recent advancesAbility to make an optimal immune response to vaccines and infectious agents declines with age in humans and animal models. Recent advances have shown intrinsic B cell defects in aged mice and humans, including decreases in Ig class switch recombination (CSR), activation-induced cytidine deaminase (AID), and E47 transcription factor. Effects on somatic hypermutation (SHM) have been varied depending on the system studied. Increase of AID in mice has shown improved CSR but not SHM. The reported microarray analysis of human B cell subsets may now be used to delineate B cell defects with aging and all the advances presented should lead to selecting agents for improved immune response in the elderly.

Causes, consequences, and reversal of immune system aging

“…B cell number in mice is unchanged by aging, but in human peripheral blood their absolute number is reduced (51). This decline is likely due to decreased numbers of IgM + memory and switched memory B cells, because the total number of naive B cells remains unchanged by aging (51,52).…”

“…B cell number in mice is unchanged by aging, but in human peripheral blood their absolute number is reduced (51). This decline is likely due to decreased numbers of IgM + memory and switched memory B cells, because the total number of naive B cells remains unchanged by aging (51,52). Human and murine B cells also exhibit impaired class switch recombination, which has been attributed to decreased induction of activation-induced cytidine deaminase (AID) enzyme (53).…”

“…Human and murine B cells also exhibit impaired class switch recombination, which has been attributed to decreased induction of activation-induced cytidine deaminase (AID) enzyme (53). In view of the critical role played by CD4 + T cells in orchestrating the immune response, some of the age-related deficiencies observed in B cells (51,53,54), which include a reduction in the number of plasmablasts that develop in response to influenza vaccination (55) and the production of poor-quality antibodies to carbohydrate antigens (56)(57)(58), may occur secondary to T cell deficiencies.…”

A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice

“…[6][7][8]36 Thus, ABCs may emerge as the product of altered B lymphopoiesis in the aged. Alternatively, they might reflect the lifelong accumulation of cells generated at low rates from existing mature compartments.…”

Augmentation of Primary Influenza A Virus-Specific CD8+ T Cell Responses in Aged Mice through Blockade of an Immunoinhibitory Pathway

“…They show an increased susceptibility to infectious agents and decreased responsiveness to vaccines due to global impairments of their immune system that affect both innate and adaptive responses. Primary B cell responses in the elderly are commonly low and short-lived (1). In mice, formation of germinal centers is decreased, resulting in Abs with low affinity and reduced long-term survival of Ab forming cells (2).…”