DOI: 10.4049/jimmunol.165.3.1438. The Role of Cell Surface Receptors in the Activation of Human B Cells by Phosphorothioate Oligonucleotides

The Role of Cell Surface Receptors in the Activation of Human B Cells by Phosphorothioate Oligonucleotides

10.4049/jimmunol.165.3.1438

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

AbstractPhosphorothioate oligodeoxynucleotides (sODN) containing the CpG motif or TCG repeats induce T cell-independent polyclonal activation of human B cells. To elucidate the mechanism of this response, the role of cell surface receptors was investigated. Sepharose beads coated with stimulatory but not nonstimulatory sODNs induced B cell proliferation comparably with soluble sODNs. The B cell stimulatory activity of Sepharose-bound sODN did not result from free sODN released from the beads since media incubated with coated beads were inactive. Using FITC-labeled sODNs as probes, binding to human B cells could be detected by flow cytometry. Binding was rapid, saturable, initially temperature independent, but with a rapid off-rate. Competition studies indicated that both stimulatory sODNs and minimally stimulatory sODNs bound to the same receptor. By contrast, phosphodiester oligonucleotides with the same nucleotide sequence as sODNs and bacterial DNA inhibited the binding of sODNs to B cells minimally. Charge appeared to contribute to the binding of sODNs to B cells since binding of sODNs was competitively inhibited by negatively charged molecules, including fucoidan, poly I, and polyvinyl sulfate. These data indicate that human B cells bind sODNs by a receptor-mediated mechanism that is necessary but not sufficient for polyclonal activation.

Bibliography

Liang, H., Reich, C. F., Pisetsky, D. S., & Lipsky, P. E. (2000). The Role of Cell Surface Receptors in the Activation of Human B Cells by Phosphorothioate Oligonucleotides. The Journal of Immunology, 165(3), 1438â1445.

Authors 4

Hua Liang (first)
Charles F. Reich (additional)
David S. Pisetsky (additional)
Peter E. Lipsky (additional)

References 33 Referenced 29

Dates

Type	When
Created	11 years, 4 months ago (April 22, 2014, 5:16 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 2, 2025, 1:04 p.m.)
Indexed	4 months, 3 weeks ago (March 31, 2025, 12:26 a.m.)
Issued	25 years ago (Aug. 1, 2000)
Published	25 years ago (Aug. 1, 2000)
Published Print	25 years ago (Aug. 1, 2000)

Funders 0

None

BibTeX

@article{Liang_2000, title={The Role of Cell Surface Receptors in the Activation of Human B Cells by Phosphorothioate Oligonucleotides}, volume={165}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.165.3.1438}, DOI={10.4049/jimmunol.165.3.1438}, number={3}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Liang, Hua and Reich, Charles F. and Pisetsky, David S. and Lipsky, Peter E.}, year={2000}, month=aug, pages={1438–1445} }

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  "abstract": "<jats:title>Abstract</jats:title><jats:p>Phosphorothioate oligodeoxynucleotides (sODN) containing the CpG motif or TCG repeats induce T cell-independent polyclonal activation of human B cells. To elucidate the mechanism of this response, the role of cell surface receptors was investigated. Sepharose beads coated with stimulatory but not nonstimulatory sODNs induced B cell proliferation comparably with soluble sODNs. The B cell stimulatory activity of Sepharose-bound sODN did not result from free sODN released from the beads since media incubated with coated beads were inactive. Using FITC-labeled sODNs as probes, binding to human B cells could be detected by flow cytometry. Binding was rapid, saturable, initially temperature independent, but with a rapid off-rate. Competition studies indicated that both stimulatory sODNs and minimally stimulatory sODNs bound to the same receptor. By contrast, phosphodiester oligonucleotides with the same nucleotide sequence as sODNs and bacterial DNA inhibited the binding of sODNs to B cells minimally. Charge appeared to contribute to the binding of sODNs to B cells since binding of sODNs was competitively inhibited by negatively charged molecules, including fucoidan, poly I, and polyvinyl sulfate. These data indicate that human B cells bind sODNs by a receptor-mediated mechanism that is necessary but not sufficient for polyclonal activation.</jats:p>",
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