当前位置: X-MOL 学术J. Exp. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
B cell–derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2017-11-06 , DOI: 10.1084/jem.20170580
Tanvi Arkatkar 1 , Samuel W. Du 1 , Holly M. Jacobs 1 , Elizabeth M. Dam 2 , Baidong Hou 3 , Jane H. Buckner 2 , David J. Rawlings 1, 4, 5 , Shaun W. Jackson 1, 5
Affiliation  

Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell–derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell–derived IL-6 abrogates spontaneous GC formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFN-γ, consistent with the critical roles for B cell–intrinsic IFN-γ receptor signals in driving autoimmune GC formation. Together, these findings identify a key mechanism whereby B cells drive autoimmunity via local IL-6 production required for TFH differentiation and autoimmune GC formation.



中文翻译:

B细胞来源的IL-6在系统性自身免疫过程中启动自发的生发中心形成

最近的研究已经确定了B细胞在引发系统性红斑狼疮(SLE)和其他疾病的自身免疫生发中心(GC)中的关键作用。但是,B细胞促进T细胞耐受性丧失的机制尚不完全清楚。活化的B细胞产生白介素6(IL-6),这是一种促炎性细胞因子,可促进T卵泡辅助物(T FH)细胞分化。尽管B细胞IL-6的产生与体液自身免疫疾病的严重程度相关,但据我们所知,是否需要B细胞衍生的IL-6触发自身免疫GC。在这里,我们报告了一个出乎意料的发现,即缺乏B细胞的IL-6消除了小鼠SLE中自发的GC形成,从而导致了类转换自身抗体的丧失和对系统自身免疫的保护。从机理上讲,IFN-γ增强了B细胞IL-6的产生,这与B细胞固有的IFN-γ受体信号在驱动自身免疫GC形成中的关键作用相一致。在一起,这些发现确定了一种关键机制,其中B细胞通过T FH分化和自身免疫GC形成所需的局部IL-6产生来驱动自身免疫。

更新日期:2017-11-06
down
wechat
bug