B-cell diversity decreases in old age and is correlated with poor health status.

Older people suffer from a decline in immune system, which affects their ability to respond to infections and to raise efficient responses to vaccines. Effective and specific antibodies in responses from older individuals are decreased in favour of non-specific antibody production. We investigated the B-cell repertoire in DNA samples from peripheral blood of individuals aged 86-94 years, and a control group aged 19-54 years, using spectratype analysis of the IGHV complementarity determining region (CDR)3. We found that a proportion of older individuals had a dramatic collapse in their B-cell repertoire diversity. Sequencing of polymerase chain reaction products from a selection of samples indicated that this loss of diversity was characterized by clonal expansions of B cells in vivo. Statistical analysis of the spectratypes enabled objective comparisons and showed that loss of diversity correlated very strongly with the general health status of the individuals; a distorted spectratype can be used to predict frailty. Correlations with survival and vitamin B12 status were also seen. We conclude that B-cell diversity can decrease dramatically with age and may have important implications for the immune health of older people. B-cell immune frailty is also a marker of general frailty.

Antibody quality in old age.

There is very little change in the quantity of antibodies people produce, of any isotype, with age. However, there is a change in the quality of the antibody response. Older people produce fewer antibodies that are specific for the activating pathogen or vaccine. At the same time, the number of nonspecific antibodies increases. Quite often these antibodies have self-reactivity (e.g., anti-dsDNA). The appearance of these antibodies is not associated with pathogenic autoimmune disease, although it is true that the incidence of some autoimmune diseases increases with age. The authors postulate that the process of antibody affinity maturation is compromised in old age. No evidence was found that the process of hypermutation is compromised with age. However, using graph theory to study the dynamics of a germinal center selection process, a decrease in the extent of selection occurring in the germinal centers of mucosal tissue was observed with age. This is a tissue-specific phenomenon because the decrease was not seen in the germinal centers of spleen. Because selection of highly specific cells in the germinal center depends on a number of factors (number and quality of founder cells, help from T cells, and follicular dendritic cells) these need to be investigated further to determine what is needed to improve the affinity mutation process.