Lambert P H, Dixon F J
Clin Exp Immunol. 1970 Jun;6(6):829-39.
Antinuclear antibodies could be induced in young NZB/W mice long before the natural occurrence of such antibodies by immunization with heat denatured DNA coupled to methylated bovine serum albumin (DNA m BSA). While induction of antinuclear antibodies was possible in several strains of mice (NZB/W, A/J, DBA/2, CBA and AKR), NZB/W mice had by far the highest titre of antibody. A genetic determination of this immune hyperreactivity to DNA was suggested by study of the parental strains. The NZW mice which have a low incidence of spontaneously occurring antinuclear antibody made as much antinuclear antibody upon immunization with DNA m BSA as did the NZB/W mice, while NZB mice which develop naturally a moderate incidence of antinuclear antibody responded relatively poorly to immunization. It seemed possible that while the native hyperreactivity of NZB/W mice to DNA might be inherited from the NZW parent, the antigenic stimulus calling forth the anti-DNA response might be transmitted from the NZB parent. A possible source of this stimulus might be a viral infection such as that caused by the leukemia virus found in NZB mice which might liberate unusual amounts or kinds of host nuclear antigens or provide viral nucleic acid antigens. In support of this, induced neonatal infection of NZB/W mice with Polyoma virus markedly enhanced their antinuclear antibody response. Also, neonatal thymectomy of NZW mice which predisposes to reduced resistance to infection also enhanced antinuclear antibody formation. And finally, Statolon treatment designed to increase and maintain interferon levels in both normal and thymectomized NZW mice reduced antinuclear antibody formation.
通过用与甲基化牛血清白蛋白偶联的热变性DNA（DNA - m BSA）免疫，可在年轻的NZB/W小鼠中早在天然出现此类抗体之前就诱导出抗核抗体。虽然在几种小鼠品系（NZB/W、A/J、DBA/2、CBA和AKR）中都可能诱导出抗核抗体，但NZB/W小鼠的抗体滴度迄今为止是最高的。通过对亲本品系的研究提示了这种对DNA免疫高反应性的遗传决定因素。自发产生抗核抗体发生率低的NZW小鼠在用DNA - m BSA免疫后产生的抗核抗体与NZB/W小鼠一样多，而天然产生抗核抗体发生率中等的NZB小鼠对免疫的反应相对较差。似乎有可能，虽然NZB/W小鼠对DNA的天然高反应性可能是从NZW亲本遗传而来，但引发抗DNA反应的抗原刺激可能是从NZB亲本传递而来。这种刺激的一个可能来源可能是病毒感染，例如在NZB小鼠中发现的白血病病毒引起的感染，它可能释放异常数量或种类的宿主核抗原或提供病毒核酸抗原。支持这一点的是，用多瘤病毒对NZB/W小鼠进行诱导性新生期感染显著增强了它们的抗核抗体反应。此外，使NZW小鼠易患感染抵抗力降低的新生期胸腺切除术也增强了抗核抗体的形成。最后，旨在提高和维持正常及胸腺切除的NZW小鼠中干扰素水平的Statolon治疗减少了抗核抗体的形成。
