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

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 t...

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Bibliographic Details
Published in:The Journal of experimental medicine 2004-06, Vol.199 (11), p.1577-1584
Main Authors: Hoyer, Bimba F, Moser, Katrin, Hauser, Anja E, Peddinghaus, Anette, Voigt, Caroline, Eilat, Dan, Radbruch, Andreas, Hiepe, Falk, Manz, Rudolf A
Format: Article
Language:English
Subjects:
Animals
Autoimmune Diseases - etiology
Autoimmune Diseases - immunology
Bromodeoxyuridine - metabolism
Chronic Disease
DNA - immunology
Female
Membrane Glycoproteins - analysis
Mice
Mice, Inbred NZB
Ovalbumin - immunology
Plasma Cells - physiology
Proteoglycans - analysis
Syndecans
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Summary: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20040168