Genetic analysis of the role of the PI3K signalling in humoral immunity

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Antibodies are produced by B lymphocytes when they differentiate into plasma cells following exposure to antigen. Antibodies are proteins that are key mediators of immunity required to protect us from pathogenic micro-organisms such as bacteria, fungi and viruses. The production of potent antibodies is central to immunity and the principle of vaccination and it has been known for many decades that during the course of an infection the quality of antibodies produced increases. Revealing the mechanism by which this takes place may provide information which will aid in vaccine design. The study of B lymphocytes in health and disease is directly relevant to our attempts to improve vaccine design; to develop new treatments for autoimmune disease; and to develop therapies to combat B cell malignancies. This project seeks to uncover the basic mechanisms that control the development and function of B cells when they are activated. The research will use genetic models in which the function of individual genes that we propose to be vital for antibody production is specifically switched off. This can be achieved in a specific cell type or at a particular stage of the immune response. By deleting candidate genes in specific cells or at specific times and testing the consequences for B cell differentiation and the ability to produce and sustain antibody production we will obtain good evidence for the function of the genes.