Artikel
Analyzing pathogenic (double-strand DNA reactive) plasma cells via histology
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Autoren
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Oliver Winter
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Melissa Schablowski
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Stephanie Musiol
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, 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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Qingyu Cheng
- Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Falk Hiepe
- Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie der Charité - Universitätsmedizin Berlin und Deutsches RheumaForschungszentrum Berlin - ein Institut der Leibniz-Gemeinschaft, Berlin
| Veröffentlicht: | 12. September 2014 |
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Gliederung
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Background: Long-lived plasma cells (LLPCs) maintain humoral immunological memory via continuous secretion of antibodies. They reside in alternative multi-component-plasma-cell-niches that are composed of a stromal and a varying hematopoietic niche component. Plasma cells that experienced different activation routes and co-stimulatory signals during their generation can migrate differently, express different receptors and thus may preferentially associate with specific niches. Although the plasma cell niche is discussed as promising target for the (specific) depletion of refractory autoreactive memory plasma cells in the treatment of autoimmune diseases like Systemic Lupus Erythematosus (SLE), methodical limitations hampered comparative and detailed analyses of the niches for pathogenic and protective plasma so far.
Methods: We established a method forthe histological analysis of autoreactive (dsDNA specific) plasma cells.In spleen and bone marrow of SLE mouse models (NZB/W and BcN/LmoJ) and healthy controls (C57BL/6) dsDNA specific plasma cells were identified by immunofluorescence staining and confocal microscopy,discriminated according to their immunoglobulin (Ig) class (IgA, IgG, IgM) and proliferating short-lived PCs (SLPCs) were distinguished from LLPCs by incorporation of EdU. For comparative studies between selfreactive pathogenic (dsDNA) and vaccine induced “protective” (ovalbumin) plasma cells we established a parallel staining for both antigens.
Results: DsDNA specific plasma cells were found in spleen and bone marrow of autoimmune mice but only few in the organs of healthy controls matching previous EliSpot data. DsDNA SLPCs and LLPCs, as well as IgA, IgG andIgM PCs that differently contribute to the pathogenesis of SLE were well distinguishable. Moreover dsDNA PCs showed no false cross reactivity with ovalbumin and the distribution of the different dsDNA and ovalbumin plasma cell sub populations within the organs could be assessed.
Conclusion: The histological analysis of dsDNA specific PCs allows comparative and detailed investigations of cellular components and molecular factors in the niche of autoreactive and “protective” plasma cells – for both, LLPCs and SLPCs. Furthermore, treatment regimes can be evaluated in detail for their effects on plasma cell sub populations and niche components. We therefore believe this novel method gives a valuable tool in the hands of researchers and clinicians and may help to characterize alternative niches and specifically target pathogenic plasma cells.
