Deborah Dunn-Walters, PhD
Reader in Immunology
Postgraduate (Research Degree) Welfare Officer (Division of Immunology, Infection and Inflammatory Disease)
Chair, Mechanisms of Ageing section of Ageing Research At King's (ARK)
Tel: +44(0) 20 7188 3067
We have extensive experience in B cell repertoire analysis, and molecular events involving the immunoglobulin gene during B cell development. We combine traditional molecular biology techniques, including high throughput sequencing of B cell repertoire, with novel mathematical analyses to devise new ways of investigating the humoral immune system.
Our particular interest is in research into ageing. Loss of immune system function with age results in the phenomenon termed “Immunosenescence.” This is associated with increased infectious disease morbidity and mortality, poor responses to vaccination, declines in established protective immunity, and increased incidence of autoimmune disorders. Until recently, most age-associated immune failures had been attributed to changes in T cell populations. However, there are many other changes in the immune system and, as data accumulate to show that B cells have a critical role in antigen presentation and regulation - in addition to their role as antibody producers - B cells and humoral immunity becomes highly significant.
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.
A list of ongoing projects is available on the current projects page.