title: JNK regulatory molecule G5PR induces IgG autoantibody-producing plasmablasts from peritoneal B1a cells.
abstract: Peritoneal B1a cells expressing CD5 and CD11b generate autoantibody-producing precursors in autoimmune-prone mice. Previous studies show reduced JNK signaling in peritoneal B1a cells of female New Zealand Black mice and an abnormal increase of protein phosphatase 2A subunit G5PR that regulates BCR-mediated JNK signaling as a cause of autoimmunity. To investigate the mechanism regulating B1a differentiation into autoantibody-secreting plasmablasts (PBs), we applied an in vitro culture system that supports long-term growth of germinal center (GC) B cells (iGB) with IL-4, CD40L, and BAFF. Compared with spleen B2 cells, B1a cells differentiated into GC-like B cells, but more markedly into PBs, and underwent class switching toward IgG1. During iGB culture, B1a cells expressed GC-associated aicda, g5pr, and bcl6, and markedly PB-associated prdm1, irf4, and xbp1. B1a-derived iGB cells from New Zealand Black × New Zealand White F1 mice highly differentiated into autoantibody-secreting PBs in vitro and localized to the GC area in vivo. In iGB culture, JNK inhibitor SP600125 augmented the differentiation of C57BL/6 B1a cells into PBs. Furthermore, B1a cells from G5PR transgenic mice markedly differentiated into IgM and IgG autoantibody-secreting PBs. In conclusion, JNK regulation is critical to suppress autoantibody-secreting PBs from peritoneal B1a cells.
authors.affiliation: Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan;
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitabatake
authors.affiliation: Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan;
authors.forename: Miho
authors.initials: M
authors.lastname: Soma
authors.affiliation: Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan;
authors.forename: Tianli
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan;
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kuwahara
authors.affiliation: Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan;
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Fukushima
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan; and.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nojima
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan; and.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitamura
authors.affiliation: Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan; nobusaka@kumamoto-u.ac.jp.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakaguchi
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007150:Immunohistochemistry; D016131:Lymphocyte Subsets / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000166:cytology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000276:immunology; D054648:Protein Phosphatase 2 / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D054648:Protein Phosphatase 2