title: Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice.
abstract: 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.
authors.affiliation: Department for Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, D-10117 Berlin, Germany.
authors.forename: Bimba F
authors.initials: BF
authors.lastname: Hoyer
authors.forename: Katrin
authors.initials: K
authors.lastname: Moser
authors.forename: Anja E
authors.initials: AE
authors.lastname: Hauser
authors.forename: Anette
authors.initials: A
authors.lastname: Peddinghaus
authors.forename: Caroline
authors.initials: C
authors.lastname: Voigt
authors.forename: Dan
authors.initials: D
authors.lastname: Eilat
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Manz
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002908:Chronic Disease; D004247:DNA / Q000276:immunology; D005260:Female; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008814:Mice, Inbred NZB; D010047:Ovalbumin / Q000276:immunology; D010950:Plasma Cells / Q000502:physiology*; D011509:Proteoglycans / Q000032:analysis; D053667:Syndecans
chemical_list: D008562:Membrane Glycoproteins; D011509:Proteoglycans; D053667:Syndecans; D010047:Ovalbumin; D004247:DNA; D001973:Bromodeoxyuridine