Antibody against the human J chain inhibits polymeric Ig receptor-mediated biliary and epithelial transport of human polymeric IgA.
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.
Vaerman
J P
JP
Catholic University of Louvain, Institute of Cell Pathology, Unit of Experimental Medicine, Brussels, Belgium. vaerman@mexp.ucl.ac.be
Langendries
A E
AE
Giffroy
D A
DA
Kaetzel
C S
CS
Fiani
C M
CM
Moro
I
I
Brandtzaeg
P
P
Kobayashi
K
K
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001665:Binding Sites; D001692:Biological Transport; D002460:Cell Line; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007070:Immunoglobulin A / Q000737:chemistry / Q000378:metabolism*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007144:Immunoglobulin J-Chains / Q000276:immunology* / Q000502:physiology; D007668:Kidney / Q000166:cytology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011422:Propionates / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011489:Protein Denaturation; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D019056:Receptors, Polymeric Immunoglobulin / Q000187:drug effects*; D012635:Secretory Component / Q000378:metabolism
D007106:Immune Sera; D007070:Immunoglobulin A; D007140:Immunoglobulin Fab Fragments; D007144:Immunoglobulin J-Chains; D011422:Propionates; D019056:Receptors, Polymeric Immunoglobulin; D012635:Secretory Component; C034639:polymeric IgA; C029658:propionic acid