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| Mechanism and function of a newly identified CpG DNA moth in human primary B cells |
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| Author(s): Hartmann G, Krieg AM |
| Source: JOURNAL OF IMMUNOLOGY Volume: 164 Issue: 2 Pages: 944-952 Published: JAN 15 2000 |
| Times Cited: 312 References: 44 |
| Abstract: The vertebrate immune system recognizes bacterial DNA based on the presence of unmethylated CpG-dinucleotides in particular base contexts ("CpG motifs"), In contrast to mice, knowledge about CpG-mediated effects on human B cells is poor. In the present study we identify and determine an optimal human CpG motif. A phosphodiester oligonucleotide containing this motif strongly stimulated CD86, CD40, CD54, and MHC class II expression, IL-6 synthesis, and proliferation of primacy human B cells, These effects required internalization of the oligonucleotide and endosomal maturation. The molecular mechanism of action of this CpG motif was associated with the sustained induction of the NF-kappa B p50/p65 heterodimer and of the transcription-factor complex AP-1, Transcription-factor activation by CpG DNA was preceded by increased phosphorylation of the stress kinases c-Jun N-terminal kinase and p38, and of activating transcription factor-2, In contrast to CpG, signaling through the B cell receptor led to activation of extracellular receptor kinase and to phosphorylation of a different isoform of c-Jun N-terminal kinase, These studies define the structure of a highly active human CpG moth and characterize its molecular mechanism of action in primary human B cells. |
| Document Type: Article |
| Language: English |
| Reprint Address: Krieg, AM (reprint author), Univ Iowa, Dept Internal Med, 540 EMRB, Iowa City, IA 52242 USA |
Addresses:
1. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA
2. Vet Affairs Med Ctr, Iowa City, IA 52246 USA
3. CpG Immunopharmaceut GmbH, Hilden, Germany
4. CpG ImmunoPharmaceut Inc, Wellesley, MA 02481 USA |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Immunology |
| IDS Number: 273LF |
| ISSN: 0022-1767 |
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