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Plasmacytoid dendri...
Plasmacytoid dendritic cells and RNA-containing immune complexes drive expansion of peripheral B cell subsets with an SLE-like phenotype
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- Berggren, Olof (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Hagberg, Niklas, 1977- (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Alexsson, Andrei (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Weber, Gert (författare)
- Ernst Moritz Arndt Univ Greifswald, Inst Biochem, Dept Mol Struct Biol, Greifswald, Germany.
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- Rönnblom, Lars (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Eloranta, Maija-Leena (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2017-08-28
- 2017
- Engelska.
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:8
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Background Hyperactive B cells and a continuous interferon (IFN)-alpha production by plasmacytoid dendritic cells (pDCs) play a key role in systemic lupus erythematosus (SLE). We asked whether the interaction between B cells and pDCs stimulated with RNA-containing immune complexes affects peripheral B cell subsets. Methods B cells and pDCs were isolated from blood of healthy individuals and stimulated with immune complexes consisting of SLE-IgG and U1snRNP (RNA-IC). Expression of cell surface molecules as well as IL-6 and IL-10 production were determined by flow cytometry and immunoassays. Gene expression profiles were determined by a NanoString nCounter expression array. Results We found a remarkable increase of double negative CD27-IgD-B cells, from 7% within fresh CD19+B cells to 37% in the RNA-IC-stimulated co-cultures of B cells and pDCs, comparable to the frequency of double negative B cells in SLE patients. Gene expression analysis of the double negative CD27-IgD -and the CD27 + IgD-memory B cells revealed that twenty-one genes were differentially expressed between the two B cell subsets (>= 2-fold, p< 0.001). The, IL21R, IL4R, CCL4, CCL3, CD83 and the IKAROS Family Zinc Finger 2 (IKZ2) showed higher expression in the double negative CD27-IgD-B cells. Conclusion The interactions between B cells and pDCs together with RNA-containing IC led to an expansion of B cells with similar phenotype as seen in SLE, suggesting that the pDC-B cell crosstalk contributes to the autoimmune feed-forward loop in SLE.
Ämnesord
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
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