Monoclonal secretory immunoglobulin A protects mice against oral challenge with the invasive pathogen Salmonella typhimurium.
Hybridomas producing monoclonal immunoglobulin A (IgA) antibodies against Salmonella typhimurium were generated by mucosal immunization of BALB/c mice with attenuated strains of S. typhimurium and subsequent fusion of Peyer's patch lymphoblasts with myeloma cells. To test the role of secretory IgA (sIgA) in protection against Salmonella sp., we analyzed in detail the protective capacity of a monoclonal IgA, Sal4, produced in polymeric as well as monomeric forms, that is directed against a carbohydrate epitope exposed on the surface of S. typhimurium. BALB/c mice bearing subcutaneous Sal4 hybridoma tumors and secreting monoclonal sIgA into their gastrointestinal tracts were protected against oral challenge with S. typhimurium. This protection was directly dependent on specific recognition by the monoclonal IgA, since mice secreting Sal4 IgA from hybridoma tumors were not protected against a fully virulent mutant that lacks the Sal4 epitope. Although monoclonal Sal4 IgA was present in the bloodstreams and tissues of tumor-bearing mice, it did not protect against intraperitoneal challenge and did not possess complement-fixing or bacteriocidal activity in vitro. Taken together, these results indicate that secretion of sIgA alone can prevent infection by an invasive enteric pathogen, presumably by immune exclusion at the mucosal surface.
GI Cell Biology Laboratory, Children's Hospital, Boston, Massachusetts.
P
P
Michetti
M J
MJ
Mahan
J M
JM
Slauch
J J
JJ
Mekalanos
M R
MR
Neutra
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000096:biosynthesis / Q000627:therapeutic use*; D000939:Epitopes / Q000032:analysis; D005260:Female; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000382:microbiology; D011961:Receptors, Fc; D011971:Receptors, Immunologic / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; C045281:IgA receptor; D007071:Immunoglobulin A, Secretory; D011961:Receptors, Fc; D011971:Receptors, Immunologic