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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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Autores principales: Hoyer, Bimba F., Moser, Katrin, Hauser, Anja E., Peddinghaus, Anette, Voigt, Caroline, Eilat, Dan, Radbruch, Andreas, Hiepe, Falk, Manz, Rudolf A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211779/
https://www.ncbi.nlm.nih.gov/pubmed/15173206
http://dx.doi.org/10.1084/jem.20040168
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author Hoyer, Bimba F.
Moser, Katrin
Hauser, Anja E.
Peddinghaus, Anette
Voigt, Caroline
Eilat, Dan
Radbruch, Andreas
Hiepe, Falk
Manz, Rudolf A.
author_facet Hoyer, Bimba F.
Moser, Katrin
Hauser, Anja E.
Peddinghaus, Anette
Voigt, Caroline
Eilat, Dan
Radbruch, Andreas
Hiepe, Falk
Manz, Rudolf A.
author_sort Hoyer, Bimba F.
collection PubMed
description 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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spelling pubmed-22117792008-03-11 Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice Hoyer, Bimba F. Moser, Katrin Hauser, Anja E. Peddinghaus, Anette Voigt, Caroline Eilat, Dan Radbruch, Andreas Hiepe, Falk Manz, Rudolf A. J Exp Med Article 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. The Rockefeller University Press 2004-06-07 /pmc/articles/PMC2211779/ /pubmed/15173206 http://dx.doi.org/10.1084/jem.20040168 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Hoyer, Bimba F.
Moser, Katrin
Hauser, Anja E.
Peddinghaus, Anette
Voigt, Caroline
Eilat, Dan
Radbruch, Andreas
Hiepe, Falk
Manz, Rudolf A.
Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice
title Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice
title_full Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice
title_fullStr Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice
title_full_unstemmed Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice
title_short Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice
title_sort short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in nzb/w mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211779/
https://www.ncbi.nlm.nih.gov/pubmed/15173206
http://dx.doi.org/10.1084/jem.20040168
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