Authors: 
D.K. Dunn-Walters
Category: 
Invited
Conference: 
Abstract: 

There is very little change in the quantity of antibodies produced, of any isotype, with age. There is, however, a change in the quality of the antibody response. Older people produce less antibodies that are specific for the activating pathogen or vaccine. At the same time, the number of non-specific antibodies increases. Quite often these antibodies have self reactivity (such as 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.

We postulate that the process of affinity maturation is compromised in old age. Affinity maturation occurs in the germinal centre of secondary lymphoid tissue. It is the process by which an activated B cell divides, mutates its immunoglobulin genes and undergoes selection based on the affinity of the newly formed antibody for the activating antigen. We find no evidence that the clonal expansion of B cells, or the process of hypermutation, are compromised with age. However, using graph theory to study the dynamics of a germinal centre selection process, we observed a decrease in the extent of selection occurring in germinal centres of mucosal tissue with age. This is a tissue-specific phenomenon, since the decrease was not seen in the germinal centres of the spleen.

Since selection of high affinity B cells in the germinal centre depends on a number of factors (number and quality of founder cells, help from germinal centre T cells and follicular dendritic cells) these will need to be investigated further to determine what is needed to improve the affinity maturation process.

Keywords (Optional): 
immunity
antibody
affinity maturation