The overall goal of our Autoimmunity Center of Excellence proposal is to investigate mechanisms for the production of autoantibodies that contribute to the pathogenesis of SLE. Three individual projects will examine basic questions related to initial induction of autoantibodies, the B cells that produce them, cross-reactivity and regulation of autoantibody producing B cells in patients with SLE (Principal and Pilot Projects) and in patients with inflammatory arthritis that develop lupus-related autoimmunity induced by TNF inhibitors (Collaborative Project). The Administrative Core will be central to the functioning of our ACE by providing budgetary and financial oversight, by managing interactions with the clinical investigators who will be recruiting patients for the proposed translational studies, by providing biostatistical oversight and by providing logistical support to facilitate scientific interactions within the Feinstein ACE, with collaborators and with other ACE members. The Core will be co- directed by Drs Anne Davidson and Betty Diamond who have vast experience with collaborative studies and will have complementary roles in managing interactions with collaborators. In addition, the Administrative Core will be supported by an established clinical infrastructure that includes a large patient pool, well-established patient cohorts, expert clinical collaborators, IRB approved protocols for data and blood collection, an experienced biostatistics collaborator and appropriate scientific technology. The close existing relationships between all the investigators and collaborators and with our long time administrative staff should ensure smooth functioning of the Core and successful implementation of all projects.