Plasmacytoid dendritic cells and RNA-containing immune complexes drive expansion of peripheral B cell subsets with an SLE-like phenotype.
PLoS One
; 12(8): e0183946, 2017.
Article
em En
| MEDLINE
| ID: mdl-28846748
ABSTRACT
BACKGROUND:
Hyperactive B cells and a continuous interferon (IFN)-α 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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RNA
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Linfócitos B
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Lúpus Eritematoso Sistêmico
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Complexo Antígeno-Anticorpo
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article