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

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 (TL1R)4. Here, we demonstrate that the responses of B cells to LPS are also regulated by another TL1R 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 RPP105 gene revealed impaired proliferative and humoral immune responses of RPP105- deficient B cells to LPS. Using originally LPS-unresponsive Ba/F3 cells expressing exogenous TLR4 and RPP105, we demonstrate the functional cooperation between TLR4 and RPP105 in LPS-induced nuclear factor RB activation. These data suggest the existence of the TLR4-RPP105 signaling module in the LPS-induced B cell activation.