Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice

  • BF Hoyer1,

    Affiliated with

    • K Moser1,

      Affiliated with

      • AE Hauser1,

        Affiliated with

        • A Peddinghaus1,

          Affiliated with

          • C Voigt1,

            Affiliated with

            • D Eilat2,

              Affiliated with

              • A Radbruch1,

                Affiliated with

                • RA Manz1 and

                  Affiliated with

                  • F Hiepe1

                    Affiliated with

                    Arthritis Res Ther20046(Suppl 1):9

                    DOI: 10.1186/ar1051

                    Received: 16 January 2004

                    Published: 24 February 2004

                    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.

                    Declarations

                    Acknowledgement

                    Both senior authors (RAM and FH) contributed equally to this work.

                    Authors’ Affiliations

                    (1)
                    Department of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital and German Rheumatism Research Center
                    (2)
                    Department of Medicine, Hadassah University Hospital

                    Copyright

                    © BioMed Central Ltd 2004

                    Advertisement