Systemic exposure to irradiated apoptotic cells induces autoantibody production.
Systemic exposure to irradiated apoptotic cells induces autoantibody production.
复制标题
DOI：
10.1084/jem.188.2.387
复制
发表时间：
1998-07-20
期刊：
影响因子：
--
通讯作者：
Elkon KB
中科院分区：
文献类型：
--
作者：
Mevorach D;Zhou JL;Song X;Elkon KB
在凋亡性细胞死亡期间，细胞表面配体启动垂死细胞的吞噬作用。这些凋亡细胞的清除被认为在没有免疫应答的情况下发生。由于许多自身抗原位于细胞表面或凋亡泡内，我们研究了小鼠通过静脉途径暴露于同系凋亡细胞是否会诱导自身抗体产生。注射同系凋亡胸腺细胞的正常小鼠产生了抗核自身抗体、抗心磷脂抗体和抗ssDNA抗体。自身抗体水平通常低于在MRL/Faslpr小鼠中观察到的水平，并且是一过性的。令人惊讶的是，六分之六的免疫小鼠表现出免疫球蛋白G沉积在肾小球免疫后几个月。这些研究结果表明，全身暴露于凋亡细胞可以诱导正常小鼠的免疫反应，并可能有助于解释抗原选择和启动的免疫反应的疾病，其特征是增加的凋亡率，如艾滋病，并可能，系统性红斑狼疮。
During apoptotic cell death, cell surface ligands initiate phagocytosis of the dying cell. Clearance of these apoptotic cells is thought to occur without an immune response. Since a number of autoantigens are located at the cell surface or within apoptotic blebs, we examined whether exposure of mice to syngeneic apoptotic cells by the intravenous route could induce autoantibody production. Normal mice injected with syngeneic apoptotic thymocytes developed antinuclear autoantibodies and anticardiolipin and anti-ssDNA antibodies. The autoantibody levels were generally lower than those observed in MRL/Faslpr mice and were transient. Surprisingly, six out of six immunized mice demonstrated immunoglobulin G deposition in the glomeruli several months after immunization. These findings indicate that systemic exposure to apoptotic cells can induce an immune response in normal mice, and may help to explain antigen selection and initiation of the immune response in diseases characterized by increased rates of apoptosis such as AIDS and, possibly, systemic lupus erythematosus.