TP13: Molecular basis for therapy resistance of autoreactive plasma cells

Autoantibodies secreted by plasma cells contribute to the pathogenesis of autoimmune diseases, such as autoimmune hemolytic anemia, systemic lupus erythematosus (SLE), Epidermolysis bullosa acquisita (EBA) and many others. The survival of antibody-secreting plasma cells depends on signals provided by the specific micro-environment (niche) that surrounds individual plasma cells. These factors include adhesion molecules and cytokines such as CD44, IL-6, BAFF und APRIL. Survival factors produced within these niches are also expected to prevent autoreactive plasma cells to be eliminated by immunosuppressive drugs, thus leading to therapy-resistant autoantibodies that represent a therapeutic challenge in autoantibody-mediated diseases. Despite their importance, the contribution of individual signals to therapy resistance of plasma cells is not known and may differ between distinct diseases. In this project, the molecular basis underlying the environmental support for autoreactive plasma cells leading to persistent production and therapy resistance.