The Humoral Immunity and Autoimmunity Group is investigating the cellular and molecular events that regulate production and selection versus elimination of memory B cells, which is of critical importance to understand how best to harness immune responses against infection, and to mitigate against autoimmunity. Our team has recently discovered the roquin gene, a key piece in what appears to be a crucial pathway for repressing formation of lupus autoantibodies and development of diseases resembling type 1 diabetes and rheumatoid arthritis. Our research aims to illuminate the cause of these diseases and identify more specific and effective therapeutic approaches.
Our group focuses on understanding how immunological memory is generated, with a particular interest in the mechanisms that control the “quality” of the antibodies produced by our immune system. Production of high affinity and long-lived antibody responses by B cells is essential to fight infections and protect our offspring. They are also key to the success of most existing vaccinations. Autoantibodies need to be carefully selected against the risk of self-reactivity: during the process of affinity maturation, some antibodies will be randomly generated that can recognise and potentially destroy our own tissues and organs. The immune system has tolerance checkpoints in place to prevent selection of cells that will produce harmful antibodies. When these checkpoints fail, autoimmune diseases such as systemic lupus, rheumatoid arthritis and type 1 diabetes can occur.
Our recent research focuses on understanding the development and regulation of the poorly characterised subset of B cell helper T cells, known as T follicular helper cells or “TFH” cells. This work intersects with the other focus of our laboratory, which is understanding the function of Roquin, an E3 ubiquitin ligase discovered in our laboratory, that when mutated (Roquinsan) leads to accumulation of Tfh cells and autoimmunity. MicroRNA-mediated immune regulation is emerging to be central to both Tfh development and the pro-inflammatory activity of Roquinsan. Our research aims to identify better and more specific targets for the treatment of both autoimmune diseases and immunodeficiency states through improved understanding of how immunological memory is generated.