Artikel
Lamina propria of the small intestine provides survival niches for memory plasma cells
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Autoren
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Dominik Lammerding
- Medizinische Klinik mit Schwerpunkt Rheumatologie und klin. Immunologie, Charité Universitätsmedizin Berlin und Deutsches Rheumaforschungszentrum Berlin, Berlin
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Qingyu Cheng
- Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Magdalena Kraft
- Deutsches Rheumaforschungszentrum Berlin (DRFZ), Berlin
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Karolin Pollok
- Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
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Laleh Khodadadi
- Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Adriano Taddeo
- Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Andreas Radbruch
- Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
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Falk Hiepe
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Anja Hauser
- Deutsches Rheuma-Forschungszentrum und Charité Universitätsmedizin, Immundynamik, Berlin
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Bimba Franziska Hoyer
- Medizinische Klinik mit Schwerpunkt Rheumatologie und klin. Immunologie, Charité Universitätsmedizin Berlin - Deutsches Rheumaforschungszentrum Berlin, Berlin
| Veröffentlicht: | 29. August 2016 |
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Gliederung
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Background: Autoreactive long-lived plasma cells (PCs) have been shown to play a major role in the pathogenesis of systemic lupus erythematosus, the prototype of systemic autoimmunity. Lymphatic organs such as spleen and bone marrow as well as inflamed organs such as inflamed kidneys have been shown to harbor longlived memory plasma cells. These cells are refractory to therapies with cyclophosphamid but have been shown to be susceptible to proteasome inhibitors. In protective humoral memory, mucosal memory plasma cells have been shown to play an important role. In this project, the intestinal lamina propria in lupus prone NZB/W F1 mice was analyzed for the presence of longlived plasma cells.
Methods: NZB/W mice of different ages were EdU-fed for 14 days in order to quantify the frequency and number of long-lived plasma cells in the lamina propria of the small intestine. Cells were analyzed by flow cytometry for the presence of plasma cell markers (Kappa, CD138) and EdU incorporation. Elispot was used to detect the number of autoreactive plasma cells and the presence of autoreactive antibodies in cell culture supernatants was determined by ELISA.
Results: We could show here that about 80% of the small intestine PCs in aged (7 month old) NZB/W mice with symptomatic lupus nephritis are indeed long-lived memory plasma cells. Using Elispot and ELISA we could show, that within this population of intestinal plasma cells, dsDNA-specific plasma cells are included, in the majority of IgA isotype.
Conclusion: In conclusion we were able to demonstrate that the intestinal lamina propria is a major compartment for long-lived plasma cells in a mouse model for systemic lupus erythematosus.
It still needs to be shown whether the autoreactive mucosal plasma cells are also in their majority longlived and in how far they contribute to systemic autoimmunity. Further analysis is also needed with regard to their isotype, the present cytokine milieu and the role of neighboring cells. Nevertheless, the presence of this important memory plasma cell compartment has to be taken into account in considering treatment strategies and efficiency.
