Vaerman J P, Langendries A E, Giffroy D A, Kaetzel C S, Fiani C M, Moro I, Brandtzaeg P, Kobayashi K
Catholic University of Louvain, Institute of Cell Pathology, Unit of Experimental Medicine, Brussels, Belgium.
Eur J Immunol. 1998 Jan;28(1):171-82. doi: 10.1002/(SICI)1521-4141(199801)28:01<171::AID-IMMU171>3.0.CO;2-#.
To emphasize the requirement for a J chain in native polymeric immunoglobulins for their selective transport into exocrine secretions, IgG, purified from two different antisera specific for the human J chain, was shown to: (i) bind in vitro to human polymeric IgA (pIgA) by density gradient ultracentrifugation; (ii) inhibit binding in vitro of rat secretory component to human pIgA; (iii) inhibit hepatic transport of human pIgA into rat bile in vivo; and (iv) inhibit apical transcytosis of pIgA in vitro by polarized human polymeric immunoglobulin receptor (pIgR)-expressing Madin-Darby canine kidney cells. Inhibition of biliary transport increased with the molar ratio of anti-J chain antibodies against pIgA and their incubation time. Anti-J chain F(ab')2 and Fab fragments also inhibited biliary transport, excluding a role for phagocytic clearance or excessive size of the immune complexes. Anti-human-Fc alpha Fab, bound to human pIgA in complexes of larger size than those with anti-J chain Fab, did not inhibit biliary transport of human pIgA. Propionic acid-denatured human pIgA, although containing J chains, was very poorly transported into rat bile. Altogether, our data strongly support, now also by in vivo experiments, the crucial role of the J chain of native pIgA in its selective pIgR-mediated transport into secretions, as suggested long ago by in vitro data only. Recent data on J chain-knockout mice, with low IgA levels in bile and feces, cannot explain the role of the J chain in contributing to the secretory component/pIgR-binding site of normal pIgA, but otherwise agree with our study.
为强调天然聚合免疫球蛋白中J链对其选择性转运至外分泌液的必要性，从两种针对人J链的不同抗血清中纯化得到的IgG，经实验表明：(i) 通过密度梯度超速离心在体外与人聚合IgA（pIgA）结合；(ii) 在体外抑制大鼠分泌成分与人pIgA的结合；(iii) 在体内抑制人pIgA向大鼠胆汁中的肝转运；(iv) 在体外抑制极化的表达人聚合免疫球蛋白受体（pIgR）的Madin-Darby犬肾细胞对pIgA的顶端转胞吞作用。胆汁转运的抑制作用随抗J链抗体与pIgA的摩尔比及其孵育时间增加而增强。抗J链F(ab')2和Fab片段也抑制胆汁转运，排除了吞噬清除或免疫复合物过大的作用。与抗J链Fab形成的复合物相比，与更大尺寸复合物中的人pIgA结合的抗人-Fcα Fab不抑制人pIgA的胆汁转运。丙酸变性的人pIgA虽然含有J链，但向大鼠胆汁中的转运很差。总之，我们的数据有力地支持了（现在通过体内实验也支持）天然pIgA的J链在其由pIgR介导的选择性转运至分泌物中的关键作用，这一作用早在以前仅由体外数据提示。关于J链基因敲除小鼠胆汁和粪便中IgA水平低的最新数据，无法解释J链在正常pIgA的分泌成分/pIgR结合位点形成中的作用，但在其他方面与我们的研究一致。
