Burlingame R W, Rubin R L, Balderas R S, Theofilopoulos A N
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
J Clin Invest. 1993 Apr;91(4):1687-96. doi: 10.1172/JCI116378.
Autoantibodies reacting with chromatin and its components, histones and DNA, are characteristic of the human autoimmune disease SLE and drug-induced lupus, but the mechanisms of their induction remain unknown. Serial serum samples collected over short intervals from lupus-prone MRL/MP-lpr/lpr and BXSB mice were tested by ELISA on chromatin and its substructures to characterize the initial autoimmune response to these antigens. Direct binding studies demonstrated that the early autoantibodies recognized discontinuous epitopes on native chromatin and the (H2A-H2B)-DNA subnucleosome. As the immune response progressed, native DNA and other chromatin constituents generally became antigenic. Based on adsorption studies and IgG subclass restriction, antibodies to native DNA were more related to chromatin than to denatured DNA. The kinetics of autoantibody appearance and the Ig class distribution were similar to the kinetics and distribution seen in antibodies induced by immunization with an exogenous T-dependent antigen. These results are most consistent with the view that autoantibodies reacting with chromatin are generated by autoimmunization with chromatin, and antibodies to native DNA are a subset of the wide spectrum of antichromatin autoantibodies.
与染色质及其组成成分（组蛋白和DNA）发生反应的自身抗体是人类自身免疫性疾病系统性红斑狼疮（SLE）和药物性狼疮的特征，但它们的诱导机制仍不清楚。通过ELISA检测从易患狼疮的MRL/MP-lpr/lpr和BXSB小鼠在短时间间隔内采集的系列血清样本，以研究其对染色质及其亚结构的初始自身免疫反应。直接结合研究表明，早期自身抗体识别天然染色质和（H2A-H2B）-DNA亚核小体上的不连续表位。随着免疫反应的进展，天然DNA和其他染色质成分通常会变得具有抗原性。基于吸附研究和IgG亚类限制，针对天然DNA的抗体与染色质的关系比与变性DNA的关系更密切。自身抗体出现的动力学和Ig类别分布与用外源性T细胞依赖性抗原免疫诱导产生的抗体的动力学和分布相似。这些结果最符合以下观点：与染色质发生反应的自身抗体是由对染色质的自身免疫产生的，而针对天然DNA的抗体是广泛的抗染色质自身抗体谱中的一个子集。
