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

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
DOI 10.4049/jimmunol.164.2.944
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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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Crossref · 10.4049/jimmunol.164.2.944

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  • Although GTCGTT has been proposed as an optimal human TLR9 activating sequence, other sequences of CpG ODN are also activating and questions remain regarding the potency of activation through sequence context, TLR secondary structure, and cell type.

    “Although GTCGTT has been proposed as an optimal human TLR9 activating sequence, other sequences of CpG ODN are also activating and questions remain regarding the potency of activation through sequence context, TLR secondary structure, and cell type [96][97][98].”

    From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [96]

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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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