Desai D D, Krishnan M R, Swindle J T, Marion T N
Department of Microbiology and Immunology, University of Tennessee, Memphis 38163.
J Immunol. 1993 Aug 1;151(3):1614-26.
Spontaneous anti-DNA antibodies in autoimmune mice have the characteristics of antibody produced by Ag-specific, clonally selective B cell stimulation. The nature of the somatically derived antibody V region structures recurrent among spontaneous anti-DNA antibodies suggests that DNA or DNA-protein complexes may provide the antigenic stimulus for autoimmune anti-DNA antibody. In order to test this hypothesis directly, we have immunized normal, nonautoimmune-predisposed mice with complexes formed with DNA and an immunogenic, DNA-binding peptide. The highly immunogenic peptide, Fus1, forms an internal domain of a 128-amino acid ubiquitin-fusion protein from Trypanosoma cruzi. DNA-Fus1 complexes formed with native calf thymus DNA induced anti-DNA antibody in normal, nonautoimmune-predisposed mice that is similar in isotype and specificity to spontaneous anti-DNA antibody in (NZB x NZW)F1 autoimmune mice. The progressive nature of the development of dsDNA specificity in the immunized mice was also analogous to what is observed in the spontaneous anti-DNA antibody response of autoimmune (NZB X NZW)F1 mice. DNA-Fus1 immunized mice that produced IgG that bound to dsDNA had low to moderate levels of proteinuria and glomerular deposits of IgG. This experimental immunization system may be useful for understanding the immunologic basis for autoimmunity to DNA.
自身免疫小鼠中的自发性抗DNA抗体具有由抗原特异性、克隆性选择的B细胞刺激产生的抗体的特征。自发性抗DNA抗体中反复出现的体细胞衍生抗体V区结构的性质表明，DNA或DNA-蛋白质复合物可能为自身免疫性抗DNA抗体提供抗原刺激。为了直接验证这一假设，我们用与DNA和一种具有免疫原性的DNA结合肽形成的复合物免疫正常、无自身免疫倾向的小鼠。这种高度免疫原性的肽Fus1，形成了来自克氏锥虫的128个氨基酸的泛素融合蛋白的一个内部结构域。与天然小牛胸腺DNA形成的DNA-Fus1复合物在正常、无自身免疫倾向的小鼠中诱导产生抗DNA抗体，其同种型和特异性与（NZB×NZW）F1自身免疫小鼠中的自发性抗DNA抗体相似。免疫小鼠中双链DNA特异性发展的渐进性也类似于在自身免疫性（NZB×NZW）F1小鼠的自发性抗DNA抗体反应中观察到的情况。产生与双链DNA结合的IgG的DNA-Fus1免疫小鼠有低至中度的蛋白尿水平和IgG的肾小球沉积物。这个实验性免疫系统可能有助于理解针对DNA的自身免疫的免疫学基础。
