Abnormal B lymphocyte activation and function in systemic sclerosis.
Abnormal B lymphocyte activation and function in systemic sclerosis.
复制标题
DOI：
10.5021/ad.2015.27.1.1
复制
发表时间：
2015-02
影响因子：
1.6
通讯作者：
Sato S
中科院分区：
文献类型：
--
作者：
Yoshizaki A;Sato S
系统性硬化症(SSC)以组织纤维化和自身免疫为特征。虽然自身免疫与SSc临床表现之间的致病关系尚不清楚，但SSc患者表现出异常的免疫反应，包括产生疾病特异性自身抗体。以往的研究表明，B细胞除了自身抗体的产生外，还通过诱导其他免疫细胞的激活等多种功能在全身自身免疫和疾病的表达中发挥关键作用。CD19是B细胞活化的重要调节因子。最近的研究表明，SSC患者的B细胞表现出上调的CD19信号通路，在SSC小鼠模型中诱导SSC特异性自身抗体的产生。CD19转基因小鼠对自身抗原失去耐受性，并自发产生自身抗体。来自SSc患者的B细胞过度表达CD19，从而在转基因小鼠中诱导SSC特异性自身抗体的产生。此外，SSC患者表现出固有的B细胞异常，表现为慢性记忆B细胞高反应，这可能是由于CD19过度表达所致。同样，皮肤紧凑的小鼠的B细胞，也就是SSC的遗传模型，显示出CD19信号的增强。在博莱霉素诱导的SSC小鼠模型中，博莱霉素诱导的Toll样受体4的内源性配体刺激B细胞产生各种纤维化细胞因子和自身抗体。值得注意的是，CD19的缺失导致B细胞高反应性和自身抗体产生的抑制，这与纤维化的改善和B细胞产生纤维化细胞因子的平行减少有关。综上所述，这些发现表明B细胞功能改变可能导致SSC的组织纤维化和自身免疫。
Systemic sclerosis (SSc) is characterized by tissue fibrosis and autoimmunity. Although the pathogenic relationship between autoimmunity and clinical manifestations of SSc remains unknown, SSc patients display abnormal immune responses including the production of disease-specific autoantibodies. Previous studies have demonstrated that B cells play a critical role in systemic autoimmunity and disease expression through various functions such as induction of the activation of other immune cells in addition to autoantibody production. CD19 is a crucial regulator of B cell activation. Recent studies demonstrated that B cells from SSc patients showed an up-regulated CD19 signaling pathway that induced SSc-specific autoantibody production in SSc mouse models. CD19 transgenic mice lost tolerance for autoantigen and generated autoantibodies spontaneously. B cells from SSc patients exhibited an overexpression of CD19 that induced SSc-specific autoantibody production in transgenic mice. Moreover, SSc patients displayed intrinsic B cell abnormalities characterized by chronic hyper-reactivity of memory B cells, which was possibly due to CD19 overexpression. Similarly, B cells from a tight-skin mouse, a genetic model of SSc, showed augmented CD19 signaling. In bleomycin-induced SSc mouse models, endogenous ligands for toll-like receptor 4 induced by bleomycin stimulated B cells to produce various fibrogenic cytokines and autoantibodies. Remarkably, the loss of CD19 resulted in the inhibition of B cell hyper-reactivity and autoantibody production, which are associated with improvements in fibrosis and a parallel decrease in fibrogenic cytokine production by B cells. Taken together, the findings suggest that altered B cell function may result in tissue fibrosis as well as autoimmunity in SSc.
登录
查看更多内容
影响因子：
3.4
作者：
Freitas, JP;Filipe, P;Rodrigo, FG
通讯作者：
Rodrigo, FG
影响因子：
6
作者：
Hasegawa, Minoru;Hamaguchi, Yasuhito;Tedder, Thomas F.
通讯作者：
Tedder, Thomas F.
影响因子：
4.4
作者：
Fujimoto, M;Poe, JC;Tedder, TF
通讯作者：
Tedder, TF
DOI：
10.1084/jem.186.11.1923
发表时间：
1997-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Inaoki M;Sato S;Weintraub BC;Goodnow CC;Tedder TF
通讯作者：
Tedder TF
影响因子：
5.8
作者：
Manoury B;Nenan S;Leclerc O;Guenon I;Boichot E;Planquois JM;Bertrand CP;Lagente V
通讯作者：
Lagente V