B Cell Biology
B lymphocytes, or B cells, are the components of the immune system responsible for making antibodies. Antibodies are soluble proteins produced in response to the entry of foreign entities into the body (eg virus infection) and permeate through the bodily fluids to seek out and and eliminate invaders. Persistence of antibodies in the body provides long-term immunity and forms the basis of all successful vaccines. However, the destructive power of antibodies means that their production needs to be carefully controlled by the immune system. Immune responses that inadvertently produce antibodies that attack the body’s own tissues can give rise to autoimmune diseases such as lupus, rheumatoid arthritis, myasthenia gravis and haemolytic anaemia. In addition, the production of IgE antibodies against harmless substances such as food components and pollen is the major cause of asthma and other allergies.
The B Cell Biology Laboratory aims to understand how the development, activation and responses of B cells are controlled and how this impacts on antibody production in both health and disease. A major focus of the laboratory is the “germinal centre”, a specialized physiological structure that forms within lymphoid tissues such as the tonsils and spleen during an immune response. Within germinal centres, B cells undergo rapid and dramatic changes to their antibody genes that improve antibody effectiveness and are crucial for immune protection and effective vaccination. We aim to understand not only how highly protective antibodies are formulated in the germinal centre but also how the production of disease causing autoantibodies or allergic antibodies can instead result.
The laboratory employs cutting edge genetic engineering approaches to observe and understand the complex and dynamic events that control B cells. High-resolution analytical techniques including multi-parameter flow cytometry, 2-photon microscopy, immunofluorescence histology, gene array and single-cell mutation analysis are utilised to give an integrated view of B cell proliferation, survival, differentiation and migration. The central position of antigen in controlling B cell responses is a major focus of the laboratory and is facilitated through the in house production of recombinant versions of the model protein antigen hen-egg lysozyme (HEL). This approach has provided important new insights into the production of protective and pathogenic antibodies and been published in the world’s leading Immunology journals. We collaborate extensively with members of our NHMRC Program Grant team from Garvan, ANU and Monash University as well as a number of other Australian and international laboratories.