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
AUTHORS (9)
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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