The etiopathologies of autoimmune diseases are complex. A broad variety of cell types and gene products are involved. However, clinical and experimental evidence suggests that the importance of an individual factor changes during the course of the disease. Factors and cell types that induce acute autoreactivity and initiate an autoimmune disease could be distinct from those that drive a chronic course of that disease. Autoreactive immunological memory, in particular B cell and plasma cell memory, contributes to chronicity through several mechanisms. Formation of autoreactive memory B cells leads to an increase in the numbers of autoreactive cells. In comparison to naive B cells, these memory B cells show a decreased threshold for activation. Additionally, a fraction of memory B cells express the chemokine receptor CXCR3, which supports their accumulation within chronically inflamed tissues. This may allow their escape from mechanisms for induction of peripheral tolerance. Within the inflamed tissue, inflammatory cytokines and autoantigens provide activation signals that promote plasma cell differentiation and survival. The autoantibodies produced locally by these plasma cells contribute to the severity of inflammation. Together, an autoreactive loop of autoantibody-induced inflammation is formed. Another integral part of immunological memory are long-lived plasma cells. These cells provide persistent humoral antibody memory. Though not all autoantibodies are produced by long-lived plasma cells, these cells have a special impact on immune pathology. Long-lived plasma cells are relatively resistant to existing therapies of immunosuppression and continuously secrete antibodies, without need for restimulation. Long-lived plasma cells provide titers of autoantibodies even during clinically quiescent phases and after immunosuppression. These persisting autoantibody titers, though often low and not causing acute clinical symptoms, are likely to maintain a low level of chronic inflammation and progressive tissue destruction, which reduces the threshold for another break of immunological tolerance.