Autoantibodies clearly contribute to tissue inflammation in systemic lupus erythematosus. In order to therapeutically target B cells making pathogenic autoantibodies, it is necessary to identify their phenotype. It is also important to understand the defects in B cell repertoire selection that permit pathogenic autoreactive B cells to enter the immunocompetent B cell repertoire. We present the data that both marginal zone and follicular B cells can produce pathogenic autoantibodies. Moreover, we discuss how B cell survival and maturation are regulated centrally prior to antigen activation and in the periphery after antigen activation to form the repertoire that generates the spectrum of circulating antibodies.