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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References
Marrack, P. & Kappler, J. W. Cell 76, 323–332 (1994).
Messina, J. P., Gilkeson, G. S. & Pisetsky, D. S. J. Immun. 147, 1759–1764 (1991).
Bird, A. P. Trends Genet. 3, 342–347 (1987).
Bennett, R. M., Gabor, G, T. & Merritt, M. M. J. clin. Invest. 76, 2182–2190 (1985).
Zhao, Q. et al. Antisense Res. Dev. 3, 53–66 (1993).
Sano, H., Imokawa, M., Steinberg, A. D. & Morimoto, C. J. immun. 130, 187–189 (1983).
Sano, H. et al. Scand. J. immun. 30, 51–63 (1989).
Krapf, F., Herrmann, M., Leitmann, W. & Kalden, J. R. Clin. exp. immun. 75, 336–342 (1989).
Richardson, B. et al. Arth. Rheum. 33, 1665–1673 (1990).
Cardon, L. R., Burge, C., Clayton, D. A. & Karlin, S. Proc. natn. Acad. Sci. U.S.A. 91, 3799–3803 (1994).
Han, J., Zhu, Z., Hsu, C. & Finley, W. H. Antisense Res. Dev. 4, 53–65 (1994).
Krieg, A. M. Immunomethods 1, 191–202 (1992).
Crooke, S. T. A. Rev. Pharmac. Toxicol. 32, 329–376 (1992).
Milligan, J. F., Matteucci, M. D. & Martin, J. C. J. med. Chem. 36, 1923–1937 (1993).
Stein, C. A. & Cheng, Y.-C. Science 261, 1004–1012 (1993).
Bayever, E., Iversen, P., Smith, L., Spinolo, J. & Zon, G. Antisense Res. Dev. 2, 109–110 (1992).
Agrawal, S. & Tang, J. Y. Antisense Res. Dev. 2, 261–266 (1992).
Bayever, E. et al. Antisense Res. Dev. 3, 383–390 (1993).
Lisziewicz, J. et al. Proc. natn. Acad. Sci. U.S.A. 91, 7942–7946 (1994).
Wagner, R. W. Nature 372, 333–335 (1994).
Stein, C. A. & Krieg, A. M. Antisense Res. Dev. 4, 67–69 (1994).
Krieg, A. M., Gause, W. C., Gourley, M. F. & Steinberg, A. D. J. immun. 143, 2448–2451 (1989).
Matson, S. & Krieg, A. M. Antisense Res. Dev. 2, 325–336 (1992).
Leibson, H. J., Marrack, P. & Kappler, J. W. J. exp. Med. 154, 1681–1693 (1981).
DeFranco, A. L., Raveche, E. S., Asofsky, R. & Paul, W. E. J. exp. Med. 155, 1523–1536 (1982).
Klinman, D. M., Eisenberg, R. A. & Steinberg, A. D. J. immun. 144, 506–511 (1990).
Darzynkiewicz, Z., Traganos, F., Sharpless, T. & Melamed, M. R. Proc. natn. Acad. Sci. U.S.A. 73, 2881–2884 (1976).
Agrawal, S., Temsamani, J. & Tang, J. Y. Proc. natn. Acad. Sci. U.S.A. 88, 7595–7599 (1991).
Bishop, G. A. J. Immun. 147, 1107–1114 (1991).
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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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