Shimoda M, Inoue Y, Azuma N, Kanno C
Department of Applied Biochemistry, Utsunomiya University, 350 Mine-machi, Utsunomiya, Tochigi, 321-8505 Japan.
Immunology. 1999 May;97(1):9-17. doi: 10.1046/j.1365-2567.1999.00755.x.
To understand the biological function of natural immunoglobulin A (IgA) antibodies in Peyer's patches (PP), we generated IgA monoclonal antibody (mAb) clones from the PP of normal, unimmunized, specific pathogen-free BALB/c mice and examined their reactivities by enzyme-linked immunosorbent assay (ELISA). Many of these antibodies reacted with more than one antigen examined, suggesting that they were polyreactive Abs. Two mAbs agglutinated several different strains of commensal bacteria isolated from mice. To examine the genetic features of these polyreactive mAbs, the VH genes of seven different IgA mAbs were sequenced. The VH genes from the VGAM, J558 and 7183 families were compared with sequence from the mAbs with distinct VDJ rearrangements. One of the mAbs that agglutinated bacteria was encoded by a germline VH gene, but the VH region of the other polyreactive mAbs contained between seven and 11 mutated sites. No indication of antigenic selection was observed in the pattern of these mutated sites. Our results show that polyreactive IgA Abs are present in PP as a part of the normal B-cell repertoire. These polyreactive Abs may establish a natural immune homeostasis, and function as a polyreactive sensor to detect pathogenic invasion and to control immune response in the gut.
为了解派伊尔结（PP）中天然免疫球蛋白A（IgA）抗体的生物学功能，我们从正常、未免疫、无特定病原体的BALB/c小鼠的PP中产生了IgA单克隆抗体（mAb）克隆，并通过酶联免疫吸附测定（ELISA）检测它们的反应性。这些抗体中有许多与所检测的一种以上抗原发生反应，表明它们是多反应性抗体。两种mAb凝集了从小鼠分离出的几种不同共生细菌菌株。为了研究这些多反应性mAb的遗传特征，对七种不同IgA mAb的VH基因进行了测序。将来自VGAM、J558和7183家族的VH基因与具有不同VDJ重排的mAb序列进行了比较。其中一种凝集细菌的mAb由种系VH基因编码，但其他多反应性mAb的VH区域含有7至11个突变位点。在这些突变位点的模式中未观察到抗原选择的迹象。我们的结果表明，多反应性IgA抗体作为正常B细胞库的一部分存在于PP中。这些多反应性抗体可能建立天然免疫稳态，并作为一种多反应性传感器发挥作用，以检测病原体入侵并控制肠道中的免疫反应。
