POLYSPECIFIC AND AUTOREACTIVE IGA SECRETED BY HYBRIDOMAS DERIVED FROMPEYERS-PATCHES OF VOMITOXIN-FED MICE - CHARACTERIZATION AND POSSIBLE PATHOGENIC ROLE IN IGA NEPHROPATHY
L. Rasooly et al., POLYSPECIFIC AND AUTOREACTIVE IGA SECRETED BY HYBRIDOMAS DERIVED FROMPEYERS-PATCHES OF VOMITOXIN-FED MICE - CHARACTERIZATION AND POSSIBLE PATHOGENIC ROLE IN IGA NEPHROPATHY, Food and chemical toxicology, 32(4), 1994, pp. 337
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.