title: Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica.
abstract: Neuromyelitis optica (NMO) is an inflammatory disease affecting the optic nerve and spinal cord, in which autoantibodies against aquaporin 4 (AQP4) water channel protein probably play a pathogenic role. Here we show that a B-cell subpopulation, exhibiting the CD19(int)CD27(high)CD38(high)CD180(-) phenotype, is selectively increased in the peripheral blood of NMO patients and that anti-AQP4 antibodies (AQP4-Abs) are mainly produced by these cells in the blood of these patients. These B cells showed the morphological as well as the phenotypical characteristics of plasmablasts (PB) and were further expanded during NMO relapse. We also demonstrate that interleukin 6 (IL-6), shown to be increased in NMO, enhanced the survival of PB as well as their AQP4-Ab secretion, whereas the blockade of IL-6 receptor (IL-6R) signaling by anti-IL-6R antibody reduced the survival of PB in vitro. These results indicate that the IL-6-dependent B-cell subpopulation is involved in the pathogenesis of NMO, thereby providing a therapeutic strategy for targeting IL-6R signaling.
authors.affiliation: Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Chihara
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Aranami
authors.forename: Wakiro
authors.initials: W
authors.lastname: Sato
authors.forename: Yusei
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyake
authors.forename: Tomoko
authors.initials: T
authors.lastname: Okamoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ogawa
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis*; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D009471:Neuromyelitis Optica / Q000097:blood / Q000276:immunology* / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D018121:Receptors, Cytokine / Q000378:metabolism; D015398:Signal Transduction; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D051401:Aquaporin 4; D001323:Autoantibodies; D015850:Interleukin-6; D018121:Receptors, Cytokine; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000093242:Interleukin-6 Inhibitors; C496030:AQP4 protein, human; C092722:CD180 protein, human; C508600:IL6 protein, human