The current view holds that chronic autoimmune diseases are driven by the continuous activation of autoreactive B and T lymphocytes. However, despite the use of potent immunosuppressive drugs designed to interfere with this activation, the production of these autoantibodies often persists and contributes to progression of the immunopathology. In the present study, we analyzed the lifespan of (auto)antibody-secreting cells (ASC) in the spleens of NZB/W mice, a murine model of human systemic lupus erythematosus (SLE). The number of splenic ASC increased in mice aged 1–5 months and became stable thereafter. Less than 60% of the splenic antibody-secreting cells were short-lived plasmablasts, whereas 40% were non-dividing, long-lived plasma cells with a half-life of more than 6 months. In NZB/W mice and D42 immunoglobulin heavy chain 'knock-in' mice, we found that a fraction of DNA-specific plasma cells were also long-lived. Although antiproliferative immunosuppressive therapy eliminates short-lived plasmablasts, long-lived plasma cells can survive and continue to produce (auto)antibodies. Thus, long-lived, autoreactive plasma cells are a relevant target for researchers aiming to develop curative therapies for autoimmune diseases.
Both senior authors (RAM and FH) contributed equally to this work.