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

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
DOI: 10.1073/pnas.1017385108 Publication Date: 2011-02-15T09:03:40Z
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.
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