Long-lived autoreactive plasma cells drive persistent autoimmune inflammation.

Aberrant production of autoantibodies by inappropriately self-reactive plasma cells is an inherent characteristic of autoimmune diseases. Several therapeutic strategies aim to deplete the plasma cell pool, or to prevent maturation of B cells into plasma cells. However, accepted views of B-cell biology are changing; recent findings show that long-lived plasma cells refractory to immunosuppressants and B-cell depletion therapies contribute to the maintenance of humoral memory and, in autoimmunity, to autoreactive memory. As a consequence of their longevity and persistence, long-lived plasma cells can support chronic inflammatory processes in autoimmune diseases by continuously secreting pathogenic antibodies, and they can contribute to flares of symptoms. As long-lived plasma cells are not sufficiently eliminated by current therapies, these findings are extremely relevant to the development of novel concepts for the treatment of autoimmune diseases. Thus, long-lived plasma cells appear to be a promising new therapeutic target.