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.

Keywords

Affiliated Institutions

• Kobe University JP
• Multiple Sclerosis Center of Atlanta US
• National Center of Neurology and Psychiatry JP

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