B Cell Biology Lab
Our lab investigates the changes that B cells undergo during an immune response and the complex events that control these changes.
B lymphocytes – or B cells – are the components of the immune system responsible for making antibodies: soluble proteins that seek out and eliminate foreign entities in the body, like viruses. While the presence of antibodies provides long-term immunity, those that inadvertently attack the body’s own tissues can give rise to autoimmune diseases, as well as asthma and some allergies.
Our lab aims to understand how the development, activation and responses of B cells are controlled, and how this impacts antibody production in both health and disease. A major research focus of ours is the ‘germinal centre’, a specialised physiological structure that forms within lymphoid tissues during an immune response. Within germinal centres, B cells undergo rapid and dramatic changes to their antibody genes. These changes 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 germinal centres but also how the production of disease-causing autoantibodies or allergic antibodies can result instead.
Our lab employs cutting-edge genetic engineering approaches to observe and understand the complex and dynamic events that control B cells. We utilise high-resolution analytical techniques –including multi-parameter flow cytometry, two-photon microscopy, immunofluorescence histology, gene array and single-cell mutation analysis – to create an integrated view of B cell proliferation, survival, differentiation and migration.
The central position of antigens in controlling B cell responses is a major focus. We facilitate this research through the in-house production of recombinant versions of the model protein antigen hen-egg lysozyme (HEL). In turn, genetically modified mice have been produced that express versions of HEL as self-antigen and potential targets of autoimmune attack. This approach has provided important new insights into the production of protective and pathogenic antibodies, many of which have been published in the world’s leading immunology journals.
In collaboration with Australian BioResources, the lab pioneered the production of genetically modified mice using CRISPR/Cas9 technology. This has led to the formation of the MEGA facility, which has produced nearly 300 different lines of genetically modified mice for researchers at Garvan and around Australia since it opened in 2015. This work is led by Dr David Zahra in the Genomic Engineering Group and is extending the use of CRISPR/Cas9 for gene therapy and production of therapeutic monoclonal antibodies.