Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica

• DOI: 10.1073/pnas.1017385108
• Publication Date: 2011-02-15T09:03:40Z
• Authors: Norio Chihara; Toshimasa Aranami; Wakiro Sato; Yusei Miyazaki; Sachiko Miyake; Tomoko Okamoto; Masafumi Ogawa; Tatsushi Toda; Takashi Yamamura
• Keywords: Adult; Aquaporin 4; Male; Cell Survival; Interleukin-6; Neuromyelitis Optica; Plasma Cells; ADP-ribosyl Cyclase 1; Tumor Necrosis Factor Receptor Superfamily, Member 7; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Gene Expression Regulation; Antigens, CD; Humans; Female; Receptors, Cytokine; Cell Shape; Autoantibodies; Cell Proliferation; Signal Transduction

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.