凋亡细胞促进狼疮性BXSB小鼠发病的研究

徐志伟　邓鸿业　邓玉兰　邹万忠　丁桂凤 中华风湿病学杂志 2000年第6期第4卷 论著

　　【摘　要】　目的　探讨凋亡细胞在系统性红斑狼疮发病中的作用。方法　将体外诱导的凋亡胸腺细胞经腹腔注射给同基因同性别的正常C57小鼠和具有狼疮倾向的雌雄BXSB小鼠；检测血清中IgM和IgG类型的抗dsDNA抗体和抗ssDNA抗体的水平，尿蛋白浓度以及肾脏中IgG类型免疫复合物的沉积。结果　用凋亡胸腺细胞免疫后，诱导C57小鼠产生IgG类型的抗dsDNA抗体和抗ssDNA抗体；相比之下，诱导雌性BXSB小鼠产生更高水平的IgG类型抗dsDNA抗体和抗ssDNA抗体；并且使雄性BXSB小鼠的尿蛋白浓度显著升高。结论　凋亡细胞具有免疫原性，它可能是狼疮性BXSB小鼠体内自身抗原的主要来源；狼疮性遗传因素和Yaa基因能促进凋亡细胞的免疫原性和增强凋亡细胞的致肾炎作用。

　　Apoptotic cells accelerate the development of systemic lupus erythematosus in lupus-prone BXSB mice

　　XU Zhiwei　DENG Hongye　DENG Yulan

　　（Department of Immunology,Beijing Medical University,Beijing 100083,China）

　　【Abstract】　Objective　To probe into the role of apoptotic cells in the disease development of systemic lupus erythematosus.Methods　Apoptotic thymocytes injected intraperitoneally into syngeneic normal C57 mice and lupus-prone BXSB mice,and then the level of anti-dsDNA and anti-ssDNA antibodies of IgM and IgG classes,and the concentration of urine protein and immune complex of IgG class deposited in kidney were detected.Results　The apoptotic thymocytes induced the production of anti-dsDNA and anti-ssDNA antibody of IgG class in C57 mice,and their levels were higher in female BXSB mice than in male ones.The concentration of urine protein of male BXSB mice injected with apoptotic thymocytes was noticeably higher than that of the control male BXSB mice.Conclusion　Apoptotic cells have immunogenicity,and may be the major source of autoantigens in lupus BXSB mice.Lupus genetic factors and Yaa gene can potentiate the immunogenicity of apoptotic cells or accelerate their inducing the lupus nephritis.

　　【Key words】　Apoptosis;　Mice,BXSB;　Lupus erythematosus,systemic

　　现在普遍认为系统性红斑狼疮(SLE)的发病机制涉及多个环节，并受遗传因素的控制和环境的影响［1］。自身抗体的产生和免疫复合物的形成是狼疮性免疫复合物型肾炎等免疫病理改变的直接原因。动物实验结果提示，狼疮性小鼠IgG类型的抗DNA抗体是自身抗原诱导的特异性体液免疫应答的结果［2］。体内的染色质(chromatin)及核小体(nucleosome)可能是主要的自身抗原［3］，但其产生来源不清楚。最近，我们实验室发现发病的狼疮性雄性BXSB小鼠的凋亡B细胞数量异常升高［4］。另有报道，在体外SLE病人的凋亡淋巴细胞也异常增加［5］。基于上述现象，我们分别将

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