Effects of aging on B cell function

Abstract

Ability 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.

Fig. 1. Mechanism for decreased CSR in aged activated B cells

The details of this model have been determined in activated B cells from mice [34,49,51,54], but human activated B cells also share the components following and including E47 mRNA stability [29]. Activated B cells from old subjects have less IgG, CSR, AID and E47 than those from young subjects. The molecular mechanism for this is that E47 mRNA stability is lower in B cells from older mice/humans and in mice this reflects more TTP and less phosphorylated TTP in old cells binding to the 3′UTR of E47 mRNA and causing its degradation. Less phospho-p38 MAPK generates this pathway in old B cells.