Grant: Project Grant

B cells are important cells of the immune system that produce molecules called antibodies, which help protect the body from infection and disease. Equally important, however, is that the activation of these cells is tightly controlled so that B cells do not aberrantly produce antibodies which target our own tissues, as happens in autoimmune diseases. Thus, the overarching goal of my research is to identify mechanisms that control the activation of B cells. We recently identified that a secreted molecule called galectin-9 that binds to sugar molecules in association with cell surface proteins, plays an important role in the regulation of B cells. The proposal here builds on this novel finding to dissect further, how galectin-9 regulates B cell responses to limit aberrant B cell activation and development of autoimmune disease. We will examine the propensity of galectin-9 deficient mice to develop antibodies against their own tissues (autoantibodies), and how the strength of the stimuli that triggers B cell responses differs in these mice compared to wild-type mice. We will also test the idea that alterations in sugar uptake will impact B cell responses by increasing the ligands for galectin-9. Lastly, we will examine the role of this sugar-binding protein in a subset of B cells called B1 B cells, which produce protective antibodies within mucosal tissues such as the lung and gut, but which are also implicated in the development of autoimmune disease. These studies are likely to yield fundamental advances in our understanding of the immune response, how it is regulated, and how it can most effectively be modulated for therapeutic purposes.