Secretory monoclonal IgA class-switch variants against bacterial enteric pathogens in bile and intestinal secretions.
In a previous study we analyzed the molecular forms of monoclonal IgA class-switch variants (moIgA variants) and their transport into murine respiratory secretions. The aim of the present study is to characterize the transport of moIgA variants into bile and intestinal secretions so that their applicability in a passive immunization model of the gut can be evaluated. Different moIgA variants were directly isolated from IgG1 and IgG2a producing hybridoma clones specific for the same surface determinants of bacterial enteric pathogens (Salmonella typhimurium and Campylobacter jejuni) as their respective parent IgG clones. Hepatobiliary transport experiments clearly revealed the selective transport of biologically active polymeric forms of the IgA variants into the murine and rat bile after intravenous injection. Biotinylation of polymeric IgA variants prior to intravenous injection resulted in the recovery of functional, labeled SIgA. Moreover biotin-labeled polymeric IgA variant was recovered in bile with an increased molecular weight, suggesting that the secretory component had been added during passage through the liver. When IgA variant and IgG parent clones were both used in a murine backpack tumor model for passive immunization, IgA variant was selectively transported into intestinal secretions in comparison to IgG. The experimental model described here is suitable for use in comparative studies on the role of IgA and IgG with identical specificity in invasive infections of the intestinal tract.
Institute of Medical Microbiology, Hannover Medical School, Germany.
I
I
Steinmetz
P
P
Schiffmann
B
B
Brenneke
D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism*; D001692:Biological Transport; D001710:Biotin; D001826:Body Fluids / Q000378:metabolism*; D016123:Campylobacter jejuni / Q000276:immunology*; D005260:Female; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D007116:Immunization, Passive; D007070:Immunoglobulin A / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009368:Neoplasm Transplantation; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D051381:Rats; D012486:Salmonella typhimurium / Q000276:immunology*; D012635:Secretory Component / Q000378:metabolism*; D014018:Tissue Distribution
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D012635:Secretory Component; C034639:polymeric IgA; D001710:Biotin