Age effects on B cells and humoral immunity in humans

Abstract

Both humoral and cellular immune responses are impaired in aged individuals, leading to decreased vaccine responses. Although T cell defects occur, defects in B cells play a significant role in age-related humoral immune changes. The ability to undergo class switch recombination (CSR), the enzyme for CSR, AID (activation-induced cytidine deaminase) and the transcription factor E47 are all decreased in aged stimulated B cells. We here present an overview of age-related changes in human B cell markers and functions, and also discuss some controversies in the field of B cell aging.

Figure 1. Age-related changes in the percentages and numbers of B cell subsets

A. One hundred μl of blood from young (20-64 years) and elderly (≥65 years) subjects were stained to evaluate the percentages of naïve and switch memory B cells. The percentages of IgM memory (IgG−IgA−CD27+, not shown) were unchanged in young and old and together with naïve and total switch memory add up to 100%. Sixty-six young and forty-six elderly subjects were evaluated. The differences between young and elderly subjects were evaluated by the Wilcoxon test (two-tailed). p<0.05 (*), p<0.01 (**). B. Fifty young and twenty-five elderly subjects were evaluated.

Figure 1. Age-related changes in the percentages and numbers of B cell subsets

A. One hundred μl of blood from young (20-64 years) and elderly (≥65 years) subjects were stained to evaluate the percentages of naïve and switch memory B cells. The percentages of IgM memory (IgG−IgA−CD27+, not shown) were unchanged in young and old and together with naïve and total switch memory add up to 100%. Sixty-six young and forty-six elderly subjects were evaluated. The differences between young and elderly subjects were evaluated by the Wilcoxon test (two-tailed). p<0.05 (*), p<0.01 (**). B. Fifty young and twenty-five elderly subjects were evaluated.

Figure 2. Aging decreases AID and E47 mRNA expression, E47 mRNA stability and increases TTP

B cells (10⁶ cells/ml) were cultured with anti-CD40/IL-4, for 1 day (E47) or 7 days (AID), or left unstimulated. At the end of these times, cells were harvested, mRNA extracted and qPCR performed. Thirty young and thirty elderly subjects were evaluated. White columns: young; black columns, elderly. The differences between young and elderly subjects were evaluated by two-tailed Student’s t test. p<0.05 (*), p<0.01 (**).

Figure 3. The response to the seasonal influenza vaccine decreases with age

Sera were collected from 37 subjects of different ages (29 young and 8 elderly) at t0 (before vaccination) and at t28 (one month after vaccination) and analyzed by HI to evaluate antibody production to vaccine (left). B cells were isolated from the peripheral blood of the same subjects at t0 and t28 and cultured for 7 days with the influenza vaccine with which they were immunized (right). Data are from the 2008-2009 and 2009-2010 influenza seasons. Results are expressed as fold-increase after vaccination. calculated as follows: values after vaccination/values before vaccination. White columns: young; black columns, elderly.The differences between young and elderly subjects were significant at p<0.05, as evaluated by the Wilcoxon test (two-tailed).