Marion T N, Tillman D M, Jou N T
Department of Microbiology and Immunology, University of Tennessee, Memphis 38163.
J Immunol. 1990 Oct 1;145(7):2322-32.
The immunologic basis for the generation of autoantibodies that are characteristic of systemic autoimmunity in mice and humans remains obscure. Experiments directed toward the analysis of serum antibody and the cell populations that combine to generate antibody in autoimmune mice have led to the proposition that autoantibody production, including anti-DNA, results from the nonselective, polyclonal activation of B cells. The present results from the molecular analyses of anti-DNA autoantibodies from an individual (NZB x NZW)F1 autoimmune mouse, however, are inconsistent with a clonally nonselective model for autoantibody production and are most consistent with a clonally selective, Ag-driven model for anti-DNA autoantibody production. These results demonstrate that Ig V region structures contributed by germ-line V region genes; recombinational diversity, including unusual DH gene usage and DH-DH recombination; and somatic mutation during B cell clonal expansion are all important for generating antibody and presumably B cell Ig receptor specificity for nucleic acids including native, duplex DNA.
在小鼠和人类中，系统性自身免疫所特有的自身抗体产生的免疫学基础仍不清楚。针对自身免疫小鼠血清抗体及参与产生抗体的细胞群体进行分析的实验表明，包括抗DNA抗体在内的自身抗体产生是B细胞非选择性多克隆激活的结果。然而，对一只（新西兰黑鼠×新西兰白鼠）F1自身免疫小鼠的抗DNA自身抗体进行分子分析所得的当前结果，与自身抗体产生的克隆非选择性模型不一致，而与抗DNA自身抗体产生的克隆选择性、抗原驱动模型最为相符。这些结果表明，种系V区基因所贡献的Ig V区结构；重组多样性，包括不寻常的DH基因使用和DH-DH重组；以及B细胞克隆扩增过程中的体细胞突变，对于产生抗体以及推测的B细胞Ig受体对包括天然双链DNA在内的核酸的特异性都很重要。
