How do B cells control T cell pancreas infiltration?. (360G-Wellcome-085896_Z_08_Z)

Selection mechanisms in the thymus fail to remove all T cells that recognize tissue-expressed self proteins. Self-reactive T cells capable of autoimmune damage are therefore present in the periphery. Continual recirculation of such cells through blood and lymphatics poses no danger to the host. However, if such cells gain access to the self-antigen bearing tissue, immune-mediated damage becomes a possibility. Our laboratory has developed a transgenic model in which the factors that control th e entry of self-reactive T cells into the target tissue can be dissected. We have mice bearing T cells specific for a pancreatic antigen that fail to enter the pancreas. We have found that we can trigger T cell infiltration of the pancreas by a single injection of B1 cells. This proposal seeks to identify the mechanism by which B1 cells trigger tissue infiltration. We will test whether B1 cells act directly on T cells, whether they modify vessels within the tissue to allow T cell access, and whether they have an intrinsic capacity to initiate the formation of ectopic lymphoid tissue. We will also identify the timeframe in which B cell depletion is beneficial during the onset and progression of autoimmunity.