Cited by 605Immune Response and InflammationT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

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Mechanism and Function of a Newly Identified CpG DNA Motif in Human Primary B Cells

Hartmann, Gunther, Krieg, Arthur M·2000·The Journal of Immunology

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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 primary 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-κB 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 motif and characterize its molecular mechanism of action in primary human B cells.

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Authors: Hartmann, G., & Krieg, A. M.
Affiliations: University of Iowa (US)
Department of Internal Medicine, University of Iowa , Iowa City, IA 52242
ORCID: Hartmann, Gunther
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2000-01
Volume: 164
Issue: 2
Pages: 944-953
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.164.2.944
OpenAlex: W1956007715
Cited by: 605
References: 48
Citations by year: 2026: 6 · 2025: 6 · 2024: 10 · 2023: 6 · 2022: 11 · 2021: 14 · 2020: 11 · 2019: 7 · 2018: 12 · 2017: 21 · 2016: 16 · 2015: 18 · 2014: 16 · 2013: 22 · 2012: 24
FWCI: 14.65
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (P01-CA66570, P01CA066570)
National Institute of Diabetes and Digestive and Kidney Diseases (DK-25295, P30DK025295)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: B cell activation, endosomal maturation, AP-1, c-Jun N-terminal kinase, p38 MAPK, ATF2, B cell receptor signaling, interleukin-6, MHC class II expression, CD40, CD86, ICAM-1
MeSH terms: B-Lymphocytes, Base Sequence, Binding Sites, DNA, HLA-D Antigens, Humans, Hydrogen-Ion Concentration, Lymphocyte Activation, Oligodeoxyribonucleotides, Phosphorylation, Endosomes, Thionucleotides, Transcription Factors, Interleukin-6, NF-kappa B, Cyclic AMP Response Element-Binding Protein, Intercellular Adhesion Molecule-1, Transcription Factor AP-1, CpG Islands, CD40 Antigens, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Activating Transcription Factor 2

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Mechanism and Function of a Newly Identified CpG DNA Motif in Human Primary B Cells

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