Responsiveness of autoimmune and normal mice to nucleic acid antigens.
Responsiveness of autoimmune and normal mice to nucleic acid antigens.
复制标题
自身免疫小鼠和正常小鼠对核酸抗原的反应性。
作者：
M. Madaio;S. Hodder;R. Schwartz;B. Stollar
为了测试自身免疫性疾病中抗DNA抗体形成与对核酸免疫原的异常反应性有关的可能性，我们检查了正常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。自身免疫小鼠（MRL/++）对佐剂中的变性DNA甲基化BSA没有显著应答（与单独的佐剂相比）。然而，它们确实对不同于B-DNA的螺旋结构（包括poly-（dG））有反应。聚（dC）、聚（dT-dG）。poly（dC-dA）和左手Z-DNA。正常小鼠（C57 BL/6）对变性DNA有反应，用其他聚合物免疫后，产生的抗体滴度等于或高于MRL/++动物。这两种菌株都不对天然DNA有反应。所诱导的抗核酸抗体具有高度的选择性，并且仅与免疫原反应。相比之下，狼疮自身抗体和来自仅接受佐剂的正常动物的抗血清与多种核酸抗原交叉反应。这一结果以及MRL/++小鼠对核酸免疫原的应答较差的发现表明，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。
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.