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

被引：408

作者：

Chihara, Norio ^{[1
,2
]}

Aranami, Toshimasa ^{[1
,3
]}

Sato, Wakiro ^{[1
]}

Miyazaki, Yusei ^{[1
]}

Miyake, Sachiko ^{[1
,3
]}

Okamoto, Tomoko ^{[3
,4
]}

Ogawa, Masafumi ^{[3
,4
]}

Toda, Tatsushi ^{[2
]}

Yamamura, Takashi ^{[1
,3
]}

机构：

[1] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Immunol, Kodaira, Tokyo 1878502, Japan

[2] Kobe Univ, Grad Sch Med, Dept Neurol, Kobe, Hyogo 6500017, Japan

[3] NCNP, Natl Ctr Hosp, Multiple Sclerosis Ctr, Tokyo 1878551, Japan

[4] NCNP, Natl Ctr Hosp, Dept Neurol, Tokyo 1878551, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 09期

基金：

日本学术振兴会;

关键词：

neuroinflamatory disease; autoimmunity; multiple sclerosis; central nervous system; IL-6 receptor blockade; MEMORY B-CELLS; ANTI-INTERLEUKIN-6 RECEPTOR ANTIBODY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MARROW STROMAL CELLS; TRANSCRIPTION FACTOR; MULTIPLE-SCLEROSIS; MONOCLONAL-ANTIBODIES; DIAGNOSTIC-CRITERIA; BONE-MARROW; DIFFERENTIATION;

D O I：

10.1073/pnas.1017385108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：3701 / 3706

页数：6

共 43 条

[1]

BAFF selectively enhances the survival of plasmablasts generated from human memory B cells [J].