The toll-like receptor protein RP105 regulates lipopolysaccharide signaling in B cells

• Main Authors: Su, I-hsin, Ogata, Hirotaka, Nagai, Yoshinor, Akashi, Sachiko, Mecklenbräuker, Ingrid, Rajewsky, Klaus, Kimoto, Masao, Tarakhovsky, Alexander
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2011
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: https://hdl.handle.net/10356/90394; http://hdl.handle.net/10220/6799
• Institution: Nanyang Technological University

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.