title: Differential requirements of MyD88 and TRIF pathways in TLR4-mediated immune responses in murine B cells.
abstract: LPS stimulates the TLR4/Myeloid differentiation protein-2 (MD-2) complex and promotes a variety of immune responses in B cells. TLR4 has two main signaling pathways, MyD88 and Toll/IL-1R (TIR)-domain-containing adaptor-inducing interferon-β (TRIF) pathways, but relatively few studies have examined these pathways in B cells. In this study, we investigated MyD88- or TRIF-dependent LPS responses in B cells by utilizing their knockout mice. Compared with wild-type (WT) B cells, MyD88(-/-) B cells were markedly impaired in up-regulation of CD86 and proliferation induced by lipid A moiety of LPS. TRIF(-/-) B cells were also impaired in these responses compared with WT B cells, but showed better responses than MyD88(-/-) B cells. Regarding class switch recombination (CSR) elicited by lipid A plus IL-4, MyD88(-/-) B cells showed similar patterns of CSR to WT B cells. However, TRIF(-/-) B cells showed the impaired in the CSR. Compared with WT and MyD88(-/-) B cells, TRIF(-/-) B cells exhibited reduced cell division, fewer IgG1(+) cells per division, and decreased activation-induced cytidine deaminase (Aicda) mRNA expression in response to lipid A plus IL-4. Finally, IgG1 production to trinitrophenyl (TNP)-LPS immunization was impaired in TRIF(-/-) mice, while MyD88(-/-) mice exhibited increased IgG1 production. Thus, MyD88 and TRIF pathways differently regulate TLR4-induced immune responses in B cells.
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan; Toyama Prefectural Institute for Pharmaceutical Research, 17-1 Nakataikouyama, Imizu City, Toyama 939-0363, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yanagibashi
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan; JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. Electronic address: ynagai@med.u-toyama.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikutani
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Hirai
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan; Toyama Prefectural Institute for Pharmaceutical Research, 17-1 Nakataikouyama, Imizu City, Toyama 939-0363, Japan. Electronic address: takatsuk@med.u-toyama.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D007074:Immunoglobulin G; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C493487:Tlr4 protein, mouse
keywords: CSR; IL-4; Innate immunity; LPS; MyD88; TLR; TRIF