The vision of the members of the TRR130 proposal is to understand and explain the details of B cell activation and B-cell induced antibody responses, as well as their dysregulation in autoimmune diseases. New findings about the early activation steps of B cells, B cell memory responses, and B cell tolerance induction have led to a general revived interest in B cell immunology. Furthermore, new regulatory functions of B cells have recently been described and the clinical application of B-cell depleting antibodies has led to a reconsideration of the importance of B cells in autoimmune diseases. These new developments necessitate a new wave of basic B cell research to understand all of these processes. The members of this consortium also have a common research interest and expertise in autoimmune diseases and aim to study the role of B cells in these diseases. A special feature of this TRR is the combination of basic research in mouse models and of human studies, particularly in autoimmune patients. These two approaches complement each other and synergize several scientific questions. Both mouse and human are directly linked in one project where a humanized mouse model is used. This mouse, which has human immune cells in an otherwise murine organism, is used to study the role of known mutations in a human gene of an inhibitory receptor in the process of autoantibody generation. One further aim of this TRR130 is to develop new therapeutic strategies to target antibody-mediated autoimmune diseases. Although B-cell depleting antibodies, such as Rituximab, have been successfully applied in patients, it is still not possible to target antibody-secreting plasma cells. Scientists of this proposal developed one example of successful targeting of plasma cells. This new targeting strategy of plasma cells used a proteasome inhibitor, which was first successfully tested in a mouse model and will in the future be tested in systemic lupus erythematosus (SLE) patients. Our TRR130 proposal combines four locations, Erlangen, Berlin, Freiburg and Göttingen, all of which not only contribute with a strong research interest in B cell immunology but also with different expertise. The special expertise of each institution is reflected in three central projects on multiphoton microscopy in Berlin, on proteomics in Freiburg, and on genetic mouse models in Erlangen. Since we consider coordinated PhD training in B cell immunology to be important as well, we included an Integrated Research Training Group in our consortium.