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Activation of Autoreactive B cells by Interaction with CpG‐stimulated Plasmacytoid Dendritic Cells
Author(s) -
Ding Chuanlin,
Yan Jun
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.668.15
Subject(s) - microbiology and biotechnology , plasmacytoid dendritic cell , cd40 , secretion , tlr9 , b cell , immunology , tlr7 , biology , dendritic cell , toll like receptor , in vitro , immune system , innate immune system , cytotoxic t cell , antibody , gene expression , biochemistry , dna methylation , gene
Plasmacytoid dendritic cells (pDCs), specialized type I interferon (IFN) producers, play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies have demonstrated that pDCs could induce B cells to differentiate into plasma cells via secretion of type I‐IFN and IL‐6. In this study, we aimed to investigate whether pDCs could directly or indirectly modulate autoreactive anti‐small nuclear ribonucleoprotein particle (snRNP) B cell responses. In vitro studies demonstrated that pDCs synergistically up‐regulated anti‐snRNP B cell proliferation, cytokine secretion such as IFN‐γ and IL‐6, and autoAb production upon TLR‐9 agonist CpG stimulation. Neutralization of IFN‐α and IL‐6 with mAbs partially abrogated the enhanced autoreactive B cell proliferation and autoAb production mediated by pDCs. Strikingly, in vitro transwell study indicated that these effects required a direct cell‐to‐cell contact between pDCs and autoreactive B cells. The enhanced B cell proliferation and autoAb production mediated by pDCs were also dependent on the activation status of pDCs since freshly isolated pDCs did not have such function. Further studies demonstrated that CD70, but not CD40L, appeared to participate to some extent in this interaction. Thus, pDC‐mediated enhanced autoreactive B cell activation is dependent both on cell‐to‐cell contact and on the release of soluble cytokines.