Fischbach M, Rabbie J, Talal N
J Clin Invest. 1981 Oct;68(4):1036-43. doi: 10.1172/jci110326.
Sera from patients with systemic lupus erythematosus and from mice spontaneously developing lupus were subjected to isoelectric focusing by a microsucrose gradient method. The spectrotypes of human antibodies to native DNA, denatured DNA, and polyriboadenylic acid (poly A) were compared. Antibodies to native DNA and denatured DNA focused into two regions whose boundaries were pH 5.0-7.0 and pH 8.5-10.0. Antinative DNA antibodies were more homogeneous than antidenatured DNA antibodies. Anti-DNA antibodies in cryoglobulins showed more restriction than those present in serum. There was no relationship between spectrotype and pattern of disease expression. Murine antibodies to native DNA were more heterogeneous than human anti-DNA antibodies. The spectrotypes of antidenatured DNA antibodies from patients with systemic lupus erythematosus or drug induced lupus, or from an immunized rabbit, were similar. Likewise, antibodies to poly A were similar in both human and murine lupus. In contrast to anti-DNA, antibodies to poly A were restricted and focused only in the alkaline range (pH 9.5-10.0). The spectrotype of antipoly A antibodies induced by lipopolysaccharide were comparable but had an additional small band at pH 6.2. Our results suggest unique antibody spectrotypes with varying degrees of restriction for different nucleic acid antigens. Furthermore, spontaneous and induced autoantibodies have similar spectrotypes. Thus, the B cell clones producing antinucleic acid antibodies may be similar whether they are activated spontaneously, following immunization, or as a consequence of polyclonal stimulation.
采用微蔗糖梯度法对系统性红斑狼疮患者及自发患狼疮小鼠的血清进行等电聚焦。比较了人抗天然DNA、变性DNA和聚核糖腺苷酸(聚A)抗体的光谱类型。抗天然DNA和变性DNA抗体聚焦于两个区域,其边界分别为pH 5.0 - 7.0和pH 8.5 - 10.0。抗天然DNA抗体比抗变性DNA抗体更具同质性。冷球蛋白中的抗DNA抗体比血清中的抗DNA抗体表现出更多的限制性。光谱类型与疾病表达模式之间没有关系。小鼠抗天然DNA抗体比人抗DNA抗体更具异质性。系统性红斑狼疮患者、药物性狼疮患者或免疫兔的抗变性DNA抗体的光谱类型相似。同样,人狼疮和小鼠狼疮中抗聚A抗体也相似。与抗DNA不同,抗聚A抗体具有限制性,仅聚焦于碱性范围(pH 9.5 - 10.0)。脂多糖诱导的抗聚A抗体的光谱类型相当,但在pH 6.2处有一条额外的小带。我们的结果表明,针对不同核酸抗原存在具有不同程度限制性的独特抗体光谱类型。此外,自发产生的自身抗体和诱导产生的自身抗体具有相似的光谱类型。因此,产生抗核酸抗体的B细胞克隆,无论它们是自发激活、免疫后激活还是多克隆刺激的结果,可能都是相似的。