POLYSPECIFIC AND AUTOREACTIVE IGA SECRETED BY HYBRIDOMAS DERIVED FROMPEYERS-PATCHES OF VOMITOXIN-FED MICE - CHARACTERIZATION AND POSSIBLE PATHOGENIC ROLE IN IGA NEPHROPATHY

A total of 122 immunoglobulin (Ig)A-producing hybridoma clones were is olated from the Peyer's patches of vomitoxin-fed BALB/c mice and the r esultant antibodies were characterized for their antigenic specificity and pathogenic potential. When reactivity was tested against a panel consisting of DNA, sphingomyelin, thyroglobulin, collagen, casein, car diolipin and bovine serum albumin conjugates of phosphorylcholine, inu lin and trinitrophenol that were representative of self and non-self a ntigens, approximately 95% of the monoclonal IgAs bound to at least on e of the panel antigens and 80% bound to more than one antigen. The po lyspecificity of some of the monoclonal IgAs was further suggested by demonstrating the capacity of one antigen to inhibit binding of monocl onal IgA to another antigen. Protein staining and Western blotting of gradient native polyacrylamide gels, indicated that trimeric IgA predo minated in the isolated monoclonal IgAs. Repeated injections of mice w ith representative monoclonal IgAs induced microhaematuria in three of four of the clones tested but not IgA deposition in the kidney glomer ulus. In addition, three of the four monoclonal IgAs caused IgG and C3 deposition in the kidney mesangium. These and previous results sugges t that dietary vomitoxin promotes the polyclonal activation and expans ion of IgA-secreting B cells at the Peyer's patch level and that resul tant polyspecific, autoreactive IgA may contribute to kidney pathogene sis.