Project Summary Adm Core The overall goal of our Autoimmunity Center of Excellence (ACE) renewal proposal is to investigate the altered states of B cells and macrophages that contribute to the pathogenesis of SLE. Three individual projects will examine basic questions related to the role of immune cell states that are induced during periods of disease activity. The Principal Project will study the differences in B cell states between patients with active SLE, patients in long-term remission, and healthy individuals to determine which programs are associated with disease activity. The Pilot Project will determine the mechanisms by which age associated B cells acquire antigen presentation functions that amplify T cell activation. The Collaborative Project will study the activation of myeloid cells that infiltrate SLE kidneys and determine whether their presence in blood or urine precedes flare. All three projects will share samples from the same patient cohorts that include legacy ACE cohorts, a cohort of patients in long-term remission and a newly acquired prospective cohort of patients at high risk of disease flare. 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 continue to 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 established mechanism to obtain samples from patients at home or work, 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.