Madaio M P, Hodder S, Schwartz R S, Stollar B D
J Immunol. 1984 Feb;132(2):872-6.
To test the possibility that anti-DNA antibody formation in autoimmune disease is related to an exceptional responsiveness to nucleic acid immunogens, we examined the ability of normal and autoimmune strains of mice to produce antibodies after immunization with DNA and synthetic helical DNA analogues. Autoimmune mice (MRL/++) did not respond significantly to denatured DNA-methylated BSA in adjuvant (in comparison with adjuvant alone). They did, however, respond to helical structures that differed from B-DNA, including poly-(dG) . poly(dC), poly(dT-dG) . poly(dC-dA), and left-handed Z-DNA. Normal mice (C57BL/6) responded to denatured DNA and, after immunization with the other polymers, produced antibodies of equal or higher titer than those of MRL/++ animals. Neither strain responded to native DNA. The induced anti-nucleic acid antibodies were highly selective and reacted only with the immunogen. In contrast, both lupus autoantibodies and antisera from normal animals that received adjuvant alone cross-reacted with multiple nucleic acid antigens. This result, and the finding that MRL/++ mice were poor responders to nucleic acid immunogens, suggest that different clones and pathways are involved in nucleic acid-induced and spontaneous anti-DNA antibody formation.
为了检验自身免疫性疾病中抗DNA抗体的形成是否与对核酸免疫原的异常反应性有关，我们检测了正常小鼠和自身免疫性小鼠品系在用DNA和合成螺旋DNA类似物免疫后产生抗体的能力。自身免疫性小鼠（MRL/++）对佐剂中的变性DNA-甲基化牛血清白蛋白没有明显反应（与单独使用佐剂相比）。然而，它们确实对不同于B-DNA的螺旋结构有反应，包括聚（dG）·聚（dC）、聚（dT-dG）·聚（dC-dA）和左手Z-DNA。正常小鼠（C57BL/6）对变性DNA有反应，在用其他聚合物免疫后，产生的抗体效价与MRL/++动物相同或更高。两个品系对天然DNA均无反应。诱导产生的抗核酸抗体具有高度选择性，仅与免疫原发生反应。相比之下，狼疮自身抗体和仅接受佐剂的正常动物抗血清均与多种核酸抗原发生交叉反应。这一结果，以及MRL/++小鼠对核酸免疫原反应不佳的发现，表明不同的克隆和途径参与了核酸诱导的和自发的抗DNA抗体形成。
