CpG motifs in bacterial DNA trigger direct B-cell activation

@article{Krieg1995CpGMI,
  title={CpG motifs in bacterial DNA trigger direct B-cell activation},
  author={Arthur M. Krieg and Ae-Kyung Yi and Sara Matson and Thomas J. Waldschmidt and Gail A. Bishop and R M Teasdale and Gary A Koretzky and Dennis M. Klinman},
  journal={Nature},
  year={1995},
  volume={374},
  pages={546-549}
}
UNMETHYLATED CpG dinucleotides are more frequent in the gen-omes of bacteria and viruses than of vertebrates. We report here that bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides induce murine B cells to proliferate and secrete immunoglobulin in vitro and in vivo. This activation is enhanced by simultaneous signals delivered through the antigen receptor. Optimal B-cell activation requires a DNA motif in which an unmethylated CpG dinucleotide is flanked… Expand

Paper Mentions

Interventional Clinical Trial
There are four populations in Recombinant Mycobacterium tuberculosis Vaccine Freeze-dried (AEC/BC02) phase I clinical research. The clinical study adopt open research design… Expand
ConditionsTuberculosis
InterventionBiological
Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs.
  • A. Krieg, T. Wu, +6 authors H. Davis
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1998
TLDR
Depending on the CpG motif, prokaryotic DNA can be either immune-stimulatory or neutralizing, and these results have important implications for understanding microbial pathogenesis and molecular evolution and for the clinical development of DNA vaccines and gene therapy vectors. Expand
Mechanism for Recognition of CpG DNA
TLDR
This chapter focuses on the recent advances in the CpG DNA-induced activation of innate immune cells, which induces a potent immune response dominated by Th1 cell-mediated cellular immunity in animal models. Expand
CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species.
TLDR
A novel pathway of leukocytes activation triggered by CpG motifs is demonstrated, which is linked to the degradation of IkappaB and the activation of NFkappaB, which induces leukocyte gene transcription and cytokine secretion. Expand
Mechanism and Function of a Newly Identified CpG DNA Motif in Human Primary B Cells1
TLDR
The structure of a highly active human CpG motif is defined and its molecular mechanism of action in primary human B cells is characterized. Expand
Adjuvant properties of CpG oligonucleotides in primates.
  • D. Verthelyi
  • Biology, Medicine
  • Methods in molecular medicine
  • 2006
TLDR
Early results from ongoing clinical studies indicate that CpG oligonucleotides (ODN) are well tolerated and improve the immune response to microbial vaccines, and this work examines the progress in utilizing C pG ODN as adjuvants in conventional and DNA vaccines. Expand
CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma.
TLDR
Stimulatory CpG DNA motifs induced B, T, and natural killer cells to secrete cytokine more effectively than did lipopolysaccharide, suggesting immune recognition of bacterial DNA may contribute to the cytokine, as well as the antibody production characteristic of an innate inflammatory response. Expand
Differences in Macrophage Activation by Bacterial DNA and CpG-Containing Oligonucleotides1
TLDR
The structural differences between E. coli DNA and PO-ODN are assessed, which may explain the high activity of bacterial DNA on macrophages and the length dependence of the CpG ODN response was found to correlate with the presence in macrophage of a length-dependent uptake process for DNA. Expand
Direct immunologic activities of CpG DNA and implications for gene therapy.
TLDR
While this is useful in generating enhanced genetic vaccines, the opposite strategy is likely to become useful for the generation of gene therapy vectors with reduced inflammatory effects. Expand
Mitogenic synthetic polynucleotides suppress the antibody response to a bacterial polysaccharide.
TLDR
Despite in vitro and in vivo evidence of B-cell proliferation, this CpG oligo reduces PS-specific antibody responses in an animal model when given simultaneously with a bacterial polysaccharide. Expand
Cytokine induction by a bacterial DNA-specific modified base.
TLDR
The results indicate that the bacterium-specific base, in addition to the unmethylated CpG motif, triggers the mammalian immune response, and suggest that N(6)-MeA-containing DNA could be useful for cellular immunotherapy and DNA vaccine. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 28 REFERENCES
Stimulation of in vitro murine lymphocyte proliferation by bacterial DNA.
TLDR
These studies provide further evidence that DNA are not uniform in their immunologic activities likely because of their content of nonconserved structural determinants. Expand
Accumulation of guanine-cytosine-enriched low M.W. DNA fragments in lymphocytes of patients with systemic lupus erythematosus.
TLDR
It is proposed that guanine cytosine-enriched low m.w.W. DNA fragments accumulate in cells after nuclear DNA is degraded, and that these fragments may serve as a primary source of autoantigen for anti-DNA antibody production and interfere with normal cellular metabolism. Expand
A role for endogenous retroviral sequences in the regulation of lymphocyte activation.
TLDR
Because endogenous MCF expression is inducible by immune stimuli, such expression could constitute an inhibitory feedback circuit that participates in the regulation of immune homeostasis. Expand
Binding Properties of Human Anti‐DNA Antibodies to Cloned Human DNA Fragments
TLDR
Observations suggested that human anti‐dsDNA antibodies may recognize some unique structures around the G+C regions or G-C clusters of DNA. Expand
Antisense oligodeoxynucleotide phosphorothioate complementary to Gag mRNA blocks replication of human immunodeficiency virus type 1 in human peripheral blood cells.
TLDR
Based on GEM91 anti-HIV-activity, safety, and pharmacokinetic profile in animals, a clinical trial was started using this compound as an antisense oligonucleotide drug for the treatment of the acquired immunodeficiency syndrome. Expand
Selection of antisense oligonucleotides on the basis of genomic frequency of the target sequence.
TLDR
The computational tools developed in this study may help to design more efficient ASOs by decreasing their nonspecific binding activity. Expand
DNA binding to human leukocytes. Evidence for a receptor-mediated association, internalization, and degradation of DNA.
TLDR
Results support the notion that there is a common binding site for DNA on white blood cells, that the stoichiometry of the association is compatible with a ligand receptor relationship, and that this apparent receptor is responsible for the endocytosis and degradation of exogenous DNA. Expand
Comparison of cellular binding and uptake of antisense phosphodiester, phosphorothioate, and mixed phosphorothioate and methylphosphonate oligonucleotides.
TLDR
Competition studies indicated that S-oligonucleotides have an increased affinity for cell membrane oligonucleotide binding sites, because they could completely block O-oligootide binding at a molar ratio of just 0.1. Expand
Nonspecific suppression of [3H]thymidine incorporation by "control" oligonucleotides.
TLDR
These studies in mitogen-stimulated mouse spleen cells demonstrate that "control" oligonucleotides that contain thymidine can cause more than 90% inhibition of [3H]thymidine incorporation, thereby causing nonspecific inhibition of "proliferation" assays. Expand
Applications of antisense oligodeoxynucleotides in immunology and autoimmunity research
TLDR
This article focuses on the practical factors that may be important in optimizing antisense efficacy, and some genes or experimental systems may not be amenable to the antisense approach. Expand
...
1
2
3
...