IL-12p70-Dependent Th1 Induction by Human B Cells Requires Combined Activation with CD40 Ligand and CpG DNA
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- Moritz Wagner
- Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich , Munich ,
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- Hendrik Poeck
- Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich , Munich ,
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- Bernd Jahrsdoerfer
- University of Iowa Cancer Center, University of Iowa , Iowa City, IA 52242
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- Simon Rothenfusser
- Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich , Munich ,
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- Domenik Prell
- Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich , Munich ,
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- Barbara Bohle
- Department of General and Experimental Pathology, University of Vienna , Vienna ,
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- Evelyn Tuma
- Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich , Munich ,
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- Thomas Giese
- Institute of Immunology, University of Heidelberg , Heidelberg ,
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- Joachim W Ellwart
- Institute for Experimental Hematology, GSF National Research Center for Environment and Health , Munich ,
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- Stefan Endres
- Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich , Munich ,
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- Gunther Hartmann
- Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich , Munich ,
書誌事項
- 公開日
- 2004-01
- 権利情報
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- https://academic.oup.com/pages/standard-publication-reuse-rights
- DOI
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- 10.4049/jimmunol.172.2.954
- 公開者
- Oxford University Press (OUP)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>The detection of microbial molecules via Toll-like receptors (TLR) in B cells is not well characterized. In this study, we found that both naive and memory B cells lack TLR4 (receptor for LPS) but express TLR9 (receptor for CpG motifs) and produce IL-6, TNF-α, and IL-10 upon stimulation with CpG oligonucleotides (ODN), synthetic mimics of microbial DNA. Consistent with the lack of TLR4, purified B cells failed to respond to LPS. Similar to CpG ODN, CD40 ligand (CD40L) alone induced IL-6, TNF-α, and IL-10. Production of these cytokines as well as IgM synthesis was synergistically increased when both CpG ODN and CD40L were combined. Unlike IL-6, TNF-α, and IL-10, the Th1 cytokine IL-12p70 was detected only when both CpG ODN and CD40L were present, and its induction was independent of B cell receptor cross-linking. CpG ODN did not increase the capacity of CD40L-activated B cells to induce proliferation of naive T cells. However, B cells activated with CpG ODN and CD40L strongly enhanced IFN-γ production in developing CD4 T cells via IL-12. Together, these results demonstrate that IL-12p70 production in human B cells is under the dual control of microbial stimulation and T cell help. Our findings provide a molecular basis for the potent adjuvant activity of CpG ODN to support humoral immune responses observed in vivo, and for the limited value of LPS.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 172 (2), 954-963, 2004-01
Oxford University Press (OUP)