The toll-like receptor protein RP105 regulates lipopolysaccharide signaling in B cells.
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 kappaB activation. These data suggest the existence of the TLR4-RP105 signaling module in the LPS-induced B cell activation.
Ogata
H
H
Department of Immunology, Saga Medical School, Saga 849-8501, Japan.
Su
I
I
Miyake
K
K
Nagai
Y
Y
Akashi
S
S
Mecklenbräuker
I
I
Rajewsky
K
K
Kimoto
M
M
Tarakhovsky
A
A
D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D003433:Crosses, Genetic; D005091:Exons; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000954:Antigens, Surface; D008070:Lipopolysaccharides; C490500:Ly78 protein, mouse; D008565:Membrane Proteins; D016328:NF-kappa B