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Published online 1 June 2004 doi:10.1084/jem.20040168
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 11, 1577-1584
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Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice

Bimba F. Hoyer2, Katrin Moser1, Anja E. Hauser1, Anette Peddinghaus1, Caroline Voigt2, Dan Eilat3, Andreas Radbruch1, Falk Hiepe2,1, and Rudolf A. Manz1

1 Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
2 Department of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, D-10117 Berlin, Germany
3 Department of Medicine, Hadassah University Hospital, 91120 Jerusalem, Israel

Address correspondence to Rudolf A. Manz, Dept. for Humoral Immunology, German Rheumatism Research Center, Schumannstrasse 21/22, D-10117 Berlin, Germany. Phone: 49-30-28460672; Fax: 49-30-2846063; email: manz{at}drfz.de; or Falk Hiepe, Dept. of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, Schumannstrasse 20/21, D-10117 Berlin, Germany. Phone: 49-30-450-513-026; Fax: 49-30-2802-8082; email: falk.hiepe{at}charite.de

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 autoantibodies often persists and contributes to progression of the immunopathology. In the present study, we analyzed the life span of (auto)antibody-secreting cells in the spleens of NZB x NZW F1 (NZB/W) mice, a murine model of systemic lupus erythematosus. The number of splenic ASCs increased in mice aged 1–5 mo and became stable thereafter. Less than 60% of the splenic (auto)antibody-secreting cells were short-lived plasmablasts, whereas 40% were nondividing, long-lived plasma cells with a half-life of >6 mo. In NZB/W mice and D42 Ig heavy chain knock-in mice, a fraction of DNA-specific plasma cells were also long-lived. Although antiproliferative immunosuppressive therapy depleted short-lived plasmablasts, long-lived plasma cells survived and continued to produce (auto)antibodies. Thus, long-lived, autoreactive plasma cells are a relevant target for researchers aiming to develop curative therapies for autoimmune diseases.

Key Words: plasma cell • autoimmunity • SLE • antibodies • anti-DNA

F. Hiepe and R.A. Manz are senior authors and contributed equally to this work.

Abbreviations used in this paper: ASC, antibody-secreting cell; BrdU, bromodeoxyuridine; BW, body weight; SLE, systemic lupus erythematosus.


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