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 × 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.
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7 June 2004
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June 01 2004
Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice
Bimba F. Hoyer,
Bimba F. Hoyer
2Department of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, D-10117 Berlin, Germany
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Katrin Moser,
Katrin Moser
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
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Anja E. Hauser,
Anja E. Hauser
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
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Anette Peddinghaus,
Anette Peddinghaus
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
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Caroline Voigt,
Caroline Voigt
2Department of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, D-10117 Berlin, Germany
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Dan Eilat,
Dan Eilat
3Department of Medicine, Hadassah University Hospital, 91120 Jerusalem, Israel
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Andreas Radbruch,
Andreas Radbruch
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
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Falk Hiepe,
Falk Hiepe
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
2Department of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, D-10117 Berlin, Germany
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Rudolf A. Manz
Rudolf A. Manz
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
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Bimba F. Hoyer
2Department of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, D-10117 Berlin, Germany
Katrin Moser
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
Anja E. Hauser
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
Anette Peddinghaus
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
Caroline Voigt
2Department of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, D-10117 Berlin, Germany
Dan Eilat
3Department of Medicine, Hadassah University Hospital, 91120 Jerusalem, Israel
Andreas Radbruch
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
Falk Hiepe
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
2Department of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, D-10117 Berlin, Germany
Rudolf A. Manz
1Department of Humoral Immunology, German Rheumatism Research Center, D-10117 Berlin, Germany
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: [email protected]; 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: [email protected]
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.
Received:
January 27 2004
Accepted:
April 28 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2004
J Exp Med (2004) 199 (11): 1577–1584.
Article history
Received:
January 27 2004
Accepted:
April 28 2004
Citation
Bimba F. Hoyer, Katrin Moser, Anja E. Hauser, Anette Peddinghaus, Caroline Voigt, Dan Eilat, Andreas Radbruch, Falk Hiepe, Rudolf A. Manz; Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice . J Exp Med 7 June 2004; 199 (11): 1577–1584. doi: https://doi.org/10.1084/jem.20040168
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