B cells do not take up bacterial DNA: An essential role for antigen in exposure of DNA to toll-like receptor-9

Roberts, Tara L., Turner, Marian L., Dunn, Jasmyn A., Lenert, Petar, Ross, Ian L., Sweet, Matthew J. and Stacey, Katryn J. (2011) B cells do not take up bacterial DNA: An essential role for antigen in exposure of DNA to toll-like receptor-9. Immunology and Cell Biology, 89 4: 517-525. doi:10.1038/icb.2010.112

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Author Roberts, Tara L.
Turner, Marian L.
Dunn, Jasmyn A.
Lenert, Petar
Ross, Ian L.
Sweet, Matthew J.
Stacey, Katryn J.
Title B cells do not take up bacterial DNA: An essential role for antigen in exposure of DNA to toll-like receptor-9
Journal name Immunology and Cell Biology   Check publisher's open access policy
ISSN 0818-9641
Publication date 2011-05
Year available 2010
Sub-type Article (original research)
DOI 10.1038/icb.2010.112
Open Access Status File (Author Post-print)
Volume 89
Issue 4
Start page 517
End page 525
Total pages 9
Place of publication London, U.K.
Publisher Nature Publishing Group
Collection year 2011
Language eng
Formatted abstract
Murine dendritic cells (DC) and macrophages respond to bacterial CpG DNA through toll-like receptor 9 (TLR9). Although it is frequently assumed that bacterial DNA is a direct stimulus for B cells, published work does not reliably show responses of purified B cells. Here we show that purified splenic B cells did not respond to Escherichia coli DNA with induction of CD86, despite readily responding to single-stranded (ss) phosphodiester CpG oligodeoxynucleotides (ODN). This was due to a combination of weak responses to both long and double-stranded (ds) DNA. B-cell DNA uptake was greatly reduced with increasing DNA length. This contrasts with macrophages where DNA uptake and subsequent responses were enhanced with increasing DNA length. However, when DNA was physically linked to hen egg lysozyme (HEL), HEL-specific B cells showed
efficient uptake of DNA, and limited proliferation in response to the HEL–DNA complex. We propose that, in the absence of other signals, B cells have poor uptake and responses to long dsDNA to prevent polyclonal activation. Conversely, when DNA is physically linked to a B-cell receptor (BCR) ligand, its uptake is increased, allowing TLR9-dependent B-cell activation in an antigen-specific manner. We could not generate fragments of E. coli DNA by limited DNaseI digestion that could mimic the stimulatory effect of ss CpG ODN on na─▒¨ve B cells. We suggest that the frequently studied polyclonal B-cell responses to CpG ODN are relevant to therapeutic applications of phosphorothioate-modified CpG-containing ODN, but not to natural responses to foreign or host dsDNA.
& 2011 Australasian Society for Immunology Inc
Keyword B-cell activation
B-cell receptor
DNA uptake
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 5 October, 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 8 times in Scopus Article | Citations
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Created: Tue, 01 Feb 2011, 11:02:01 EST by Susan Allen on behalf of Institute for Molecular Bioscience