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The Toll-like Receptor Protein Rp105 Regulates Lipopolysaccharide Signaling in B Cells

Ogata, Hirotaka, Su, I-hsin, Miyake, Kensuke, Nagai, Yoshinori, Akashi, Sachiko, Mecklenbräuker, Ingrid, Rajewsky, Klaus, Kimoto, Masao, Tarakhovsky, Alexander·2000·The Journal of Experimental Medicine

Abstract

The susceptibility to infections induced by Gram-negative bacteria is largely determined by innate immune responses to bacteria cell wall lipopolysaccharide (LPS). The stimulation of B cells by LPS enhances their antigen-presenting capacity and is accompanied by B cell proliferation and secretion of large quantities of LPS-neutralizing antibodies. Similar to macrophages and neutrophils, the LPS-induced activation of B cells is dependent on Toll-like receptor (TLR)4. Here, we demonstrate that the responses of B cells to LPS are also regulated by another TLR protein, RP105, which is predominantly expressed on mature B cells in mice and humans. The analysis of mice homozygous for the null mutation in the RP105 gene revealed impaired proliferative and humoral immune responses of RP105-deficient B cells to LPS. Using originally LPS-unresponsive Ba/F3 cells expressing exogenous TLR4 and RP105, we demonstrate the functional cooperation between TLR4 and RP105 in LPS-induced nuclear factor κB activation. These data suggest the existence of the TLR4–RP105 signaling module in the LPS-induced B cell activation.

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Research works printed but not linked: 23

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Metadata

Authors
Ogata, H., Su, I.-H., Miyake, K., Nagai, Y., Akashi, S., Mecklenbräuker, I., Rajewsky, K., Kimoto, M., & Tarakhovsky, A.
Affiliations
  • aDepartment of Immunology, Saga Medical School, Saga 849-8501, Japan
  • bLaboratory of Lymphocyte Signaling, Institute for Genetics, University of Cologne, 50931 Cologne, Germany
  • cDepartment of Immunology, Institute for Genetics, University of Cologne, 50931 Cologne, Germany
Venue
The Journal of Experimental Medicine
Published
2000-06-26
Volume
192
Issue
1
Pages
23-30
ISSN
  • 0022-1007
  • 1540-9538
Cited by
230
References
0
Language
en

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