淋巴细胞“PLASMABLAST”增多导致视神经脊髓炎

　　日本一个研究小组日前报告说，该小组发现了视神经脊髓炎的一个致病原因。在视神经脊髓炎患者的血液中，特定的淋巴细胞会显着增加，从而产生破坏神经系统细胞的抗体。这一发现为根治视神经脊髓炎带来了希望。

　　日本国立精神和神经医疗研究中心的山村隆研究员和同事，在新一期美国《国家科学院学报》网络版上发表论文指出，他们分析了24名视神经脊髓炎患者的血样，发现其中一种名为“PLASMABLAST”的淋巴细胞比正常人和多发性硬化症患者都要多。经研究确认，这种淋巴细胞因受到免疫活性物质IL6的刺激而增多。在IL6免疫活性物质的刺激下，该淋巴细胞还会制造破坏神经系统细胞的“抗水通道蛋白4抗体”，最终引起视神经脊髓炎。

　　推荐原文出处：

　　PNAS  doi: 10.1073/pnas.1017385108

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

　　Norio Chiharaa,b, Toshimasa Aranamia,c, Wakiro Satoa, Yusei Miyazakia, Sachiko Miyakea,c, Tomoko Okamotoc,d, Masafumi Ogawac,d, Tatsushi Todab, and Takashi Yamamuraa,c,1

　　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 CD19intCD27highCD38highCD180? 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.