How to cope with pathogenic long-lived plasma cells in autoimmune diseases

Recently, it has been shown that plasma cells secreting antibodies can be long lived and as such constitute an independent component of immunological memory. They are generated in the context of memory immune reactions and migrate to the bone marrow, where they persist for years and decades. Their survival is dependent on receiving distinct signals provided by cells forming a plasma cell survival niche. They also can migrate to, and survive in, inflamed tissue. In autoimmune diseases long-lived plasma cells secreting autoantibodies provide an as yet unmet therapeutic challenge, because they are resistant to conventional treatments, in particular to immunosuppression and anti-inflammatory drugs. They are eliminated by immunoablation with antithymocyte globulin. This may be the reason why immunoablation followed by reconstitution of the patient’s immune system from haematopoietic stem cells induces long-term remissions in many patients with autoimmune diseases. However, more specific treatments for the elimination of autoreactive, long-lived plasma cells are needed, to avoid the complete temporary immunoincomptence induced by immunoablation, and to decipher the role of long-lived autoreactive plasma cells in human autoimmune diseases in more detail.