How T follicular helper cells and the germinal centre response change with age

Normal ageing is accompanied by a decline in the function of the immune system that causes an increased susceptibility to infections and an impaired response to vaccination in older individuals. This results in an increased disease burden in the aged population, even with good immunisation programmes in place. The decreased response to vaccination is partly due to the diminution of the germinal centre response with age, caused by impaired T-cell help to B cells. Within the germinal centre, T-cell help is provided by a specialised subset of CD4(+) T cells; T follicular helper (Tfh) cells. Tfh cells provide survival and selection signals to germinal centre B cells, allowing them to egress from the germinal centre and become long-live plasma cells or memory B cells, and provide life-long protection against subsequent infection. This review will discuss the cellular and molecular changes in both Tfh cells and germinal centre B cells that occur with advancing age, which result in a smaller germinal centre response and a less effective response to immunisation.