Mechanisms controlling antibody production by modulating B cell antigen receptor signalling

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This project will analyse mechanisms that regulate antibody production in health and disease. In health, antibodies are normally made exclusively against infectious agents, providing long-lasting immunity. Unknown errors in the control of antibody production result in autoimmune diseases such as systemic lupus or rheumatoid arthritis, where antibodies are made against parts of our own bodies, or result in allergies where antibodies are made against innocuous elements of our environment, or result in uncontrolled B cell accumulation in lymphoma, leukemia and myeloma. In order to develop rational, specific methods for treating these diseases, it is necessary to identify and understand the biochemical mechanisms that normally control antibody formation against infectious agents, self components, and innocuous environmental agents. The project focuses on defining the biochemical mechanisms by which the antibody-forming cells, B lymphocytes, sense infectious, innocuous, or self components. These cells carry specific receptors that bind these components and transmit signals into the B lymphocyte. The research will determine how different types of signal are transmitted by the receptor so that, normally, large amounts of antibody are made against infectious agents but very little antibody is made against self components, and that B cell accumulation is tightly limited. By identifying how the types of signals are changed, the results of this project will reveal control mechanisms that may be altered in autoimmunity, allergy, immune deficiency, or lymphoma, and that may be able to be used as drug targets to cure these diseases.