Anna Francis

Supervisor: Dr Andrew Sage

Title: Characterisation of the germinal centre response and its pathogenesis in atherosclerosis

Abstract: Atherosclerosis is a chronic inflammatory disease characterised by build up of plaques within arterial walls and can lead to heart attack and stroke. Elevated plasma low density lipoprotein (LDL) is the major risk factor and its immunogenic oxidation triggers an inflammatory response. B cells can be protective by producing natural IgM antibodies to oxidation-specific epitopes (OSEs) clearing apoptotic cells and neutralising oxidised debris.

However, recently a pathogenic function has been discovered as they produce autoantibodies and promote pathogenic T cell subsets. It has been suggested that the germinal centre (GC) response, the process by which plasma and memory B cells are formed, is pathogenically dysregulated in atherosclerosis as indicated by the upregulation of germinal centres in ApoE-/- mice, the presence of self-antigens and a local class-switched B cell response including antibodies within atherosclerotic arteries, however it is poorly understood. 

This PhD aims to characterise germinal centre responses and investigate their pathogenicity within the atherosclerotic setting. This will be conducted using atherosclerosis mouse models in combination with flow cytometry and histological techniques to compare differences between atherosclerotic and wildtype mice.