The older immune system is not as effective as it is in our younger years. We don’t make good immune response to vaccines, we catch infectious diseases more easily, and we are more likely to suffer from autoimmune diseases and cancer. There are many different aspects to the immune system that are changed with age, we look at a particular type of cell - the B cell - that produces antibodies to fight infection and helps other cells by presenting foreign antigens to them. The important gene in a B cell, the one that encodes the antibody, is unique to each B cell and its progeny. Since we have a lot of B cells, we have a lot of different immunoglobulin genes encoding a lot of different specificities for foreign antigen. Our lab is expert in analysis of these immunoglobuliln (Ig) gene repertoires.
Previous work in our lab has shown that levels of Ig gene hypermutation generally increase with age even though the rates of hypermutation in the GC remain unchanged, implying re-activation of antigen-experienced cells. The stringency of the selection process acting on these Ig genes during affinity maturation of antibodies appeared to decrease with age in mucosal secondary lymphoid tissue. We also found that B cell diversity decreases in some old people, and lack of diversity correlates with the increased appearance of clonal populations as determined by sequence analysis. Furthermore, the decrease in total B cell diversity correlates with poor health and earlier mortality. Hence our current research is continuing this work – investigating how a lack of diversity can affect specific immune responses, cell-intrinsic differences between young and aged B cells and undertaking studies of B cell repertoire composition to test theories of age-related changes in homeostatic regulation. We are identifying “ageing-specific” and “development-specific” types of antibodies in silico and cloning them for functional studies in vitro. In addition we are using the same techniques to identify antibodies of importance in vaccination, in infection and in tumours.
Faculty of Health and Medical Sciences, Duke of Kent Building, University of Surrey,
Guildford, GU2 7XH