The toll-like receptor protein RP105 regulates lipopolysaccharide signaling in B cells
Date of Issue2000
School of Biological Sciences
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 kB activation. These data suggest the existence of the TLR4–RP105 signaling module in the LPS-induced B cell activation.
DRNTU::Science::Biological sciences::Molecular biology
Journal of experimental medicine
© 2000 Rockefeller University Press. This paper was published in Journal of Experimental Medicine and is made available as an electronic reprint (preprint) with permission of Rockefeller University Press. The paper can be found at: [DOI: http://dx.doi.org/10.1084/jem.192.1.23]. One print or electronic copy may be made for personal use only. Systematic or multiple reproductions, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.