title: The atypical IκB protein IκB(NS) is important for Toll-like receptor-induced interleukin-10 production in B cells.
abstract: Although a major function of B cells is to mediate humoral immunity by producing antigen-specific antibodies, a specific subset of B cells is important for immune suppression, which is mainly mediated by the secretion of the anti-inflammatory cytokine interleukin-10 (IL-10). However, the mechanism by which IL-10 is induced in B cells has not been fully elucidated. Here, we report that IκBNS , an inducible nuclear IκB protein, is important for Toll-like receptor (TLR)-mediated IL-10 production in B cells. Studies using IκB(NS) knockout mice revealed that the number of IL-10-producing B cells is reduced in IκB(NS)(-/-) spleens and that the TLR-mediated induction of cytoplasmic IL-10-positive cells and IL-10 secretion in B cells are impaired in the absence of IκB(NS). The impairment of IL-10 production by a lack of IκB(NS) was not observed in TLR-triggered macrophages or T-cell-receptor-stimulated CD4(+) CD25(+) T cells. In addition, IκB(NS)-deficient B cells showed reduced expression of Prdm1 and Irf4 and failed to generate IL-10(+) CD138(+) plasmablasts. These results suggest that IκB(NS) is selectively required for IL-10 production in B cells responding to TLR signals, so defining an additional role for IκB(NS) in the control of the B-cell-mediated immune responses.
authors.affiliation: Department of Biology, Faculty of Science, Niigata University, Niigata, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Miura
authors.affiliation: Department of Biology, Faculty of Science, Niigata University, Niigata, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hasegawa
authors.affiliation: Department of Life Sciences, Graduate School of Science and Technology, Niigata University, Niigata, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Department of Life Sciences, Graduate School of Science and Technology, Niigata University, Niigata, Japan.
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Department of Biology, Faculty of Science, Niigata University, Niigata, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Touma
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D020672:I-kappa B Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013154:Spleen; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051193:Toll-Like Receptors; D016753:Interleukin-10
keywords: IκBNS; Toll-like receptors; interleukin-10-producing B cells