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CpG motifs in bacterial DNA trigger direct B-cell activation

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Abstract

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 by two 5' purines and two 3' pyrimidines. Oligodeoxynucleotides containing this CpG motif induce more than 95% of all spleen B cells to enter the cell cycle. These data suggest a possible evolutionary link between immune defence based on the recognition of microbial DNA and the phenomenon of 'CpG suppression' in vertebrates. The potent immune activation by CpG oligonucleotides has impli-cations for the design and interpretation of studies using 'antisense' oligonucleotides and points to possible new applications as adjuvants.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242, USA

    Arthur M. Krieg, Ae-Kyung Yi, Sara Matson, Gail A. Bishop, Rebecca Teasdale & Gary A. Koretzky

  2. Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa, 52242, USA

    Thomas J. Waldschmidt

  3. Department of Microbiology, University of Iowa College of Medicine, Iowa City, Iowa, 52242, USA

    Gail A. Bishop

  4. Department of Physiology, University of Iowa College of Medicine, Iowa City, Iowa, 52242, USA

    Gary A. Koretzky

  5. Veterans Affairs Medical Center, Iowa City, Iowa, 52246, USA

    Arthur M. Krieg & Gail A. Bishop

  6. Retroviral Immunology Section, CBER, PDA, Bethesda, Maryland, 20892, USA

    Dennis M. Klinman

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  1. Arthur M. Krieg
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  2. Ae-Kyung Yi
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  3. Sara Matson
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  4. Thomas J. Waldschmidt
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  6. Rebecca Teasdale
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  7. Gary A. Koretzky
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  8. Dennis M. Klinman
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Krieg, A., Yi, AK., Matson, S. et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374, 546–549 (1995). https://doi.org/10.1038/374546a0

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  • DOI: https://doi.org/10.1038/374546a0

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