Shimoda M, Inoue Y, Ametani A, Fujiwara J, Tsuji N M, Kurisaki J, Azuma N, Kanno C
Department of Applied Biochemistry, Utsunomiya University, Utsunomiya, Tochigi.
Immunology. 1998 Oct;95(2):200-7. doi: 10.1046/j.1365-2567.1998.00582.x.
IgA antibodies in the mucosal immune system are produced specifically to environmental antigens such as virus and bacteria, and possibly to some food components, which will provide a potential luminal antigen, DNA. To study the immune response to DNA in the gut, we established B-cell hybridomas producing IgA monoclonal antibodies (mAb) from Peyer's patches (PP) of non-immunized, non-autoimmune, specific pathogen-free BALB/c mice, and examined their specificity by enzyme-linked immunosorbent assay (ELISA). Three mAb out of 18 bound strongly to self, bacterial and synthetic DNA, with Kd of about 10-7 m. One of the three mAb also reacted with the histone component and another reacted with some mouse food component. The VH genes of these three mAb have not previously been reported to have anti-DNA specificity, and carry putative somatically mutated sites favouring DNA binding in CDR. The features resemble those of anti-DNA antibodies found in human and murine models of systemic lupus erythmatosus (SLE), and are indicative of an antigen-driven selection process. Our findings suggest that even in normal healthy animals, anti-DNA antibodies of IgA isotype can be produced in certain peripheral environments such as in PP by spontaneous antigenic stimulation.
黏膜免疫系统中的IgA抗体是专门针对环境抗原产生的，如病毒和细菌，也可能针对一些食物成分，这些成分会提供潜在的腔内抗原——DNA。为了研究肠道对DNA的免疫反应，我们从未免疫、非自身免疫、无特定病原体的BALB/c小鼠的派尔集合淋巴结（PP）中建立了产生IgA单克隆抗体（mAb）的B细胞杂交瘤，并通过酶联免疫吸附测定（ELISA）检测它们的特异性。18个mAb中有3个与自身、细菌和合成DNA强烈结合，解离常数（Kd）约为10⁻⁷m。这3个mAb中的一个还与组蛋白成分反应，另一个与一些小鼠食物成分反应。这3个mAb的重链可变区（VH）基因以前未被报道具有抗DNA特异性，并且在互补决定区（CDR）携带有利于DNA结合的推定体细胞突变位点。这些特征类似于在系统性红斑狼疮（SLE）的人类和小鼠模型中发现的抗DNA抗体，表明存在抗原驱动的选择过程。我们的研究结果表明，即使在正常健康动物中，IgA同种型的抗DNA抗体也可以在某些外周环境中，如在PP中，通过自发的抗原刺激产生。
