Little is known about the differences between B cells reactive with nuclear antigen (ANA+) and ANA- B cells in individuals with systemic lupus erythematosus (SLE) or whether the regulation of ANA+ and ANA- B cells differs between SLE patients and healthy individuals. We will study activation and transcriptional profile in ANA+ and ANA- naïve, unswitched memory and switched memory B cells in individuals with active SLE, individuals with SLE in remission and healthy individuals. We will determine the antigenic and BCR repertoire of ANA+ B cells in these three cohorts to understand B cell selection. These studies are designed to reveal if there are aspects of ANA+ B cells in SLE that makes them susceptible to a therapeutic intervention that will not affect those B cells engaged in a protective response.