Back-pack mice as a model of renal mesangial IgA dimers deposition.
Mesangial IgA in IgA nephropathy are dimers with a J chain but no poly-Ig receptor. This molecular structure has led to the hypothesis that these IgA are issued from the lamina propria of mucosal areas, reaching the kidney by way of the peripheral blood. The availability of hybridomas producing IgA dimers provided an opportunity to test this hypothesis in a new experimental model of IgA nephropathy. Mice were injected subcutaneously (back-pack mice) or intraperitoneally with hybridoma cells secreting either monoclonal IgA dimers, or monoclonal IgA monomers. The influence of immune complex formation was also tested in both these models. Renal IgA deposition was investigated 12 days after the injection of hybridoma cells. Backpack mice developed highly vascularized subcutaneous tumors. Mesangial IgA deposits were observed only in dimeric IgA hybridoma back-pack animals. No significant staining was observed in glomeruli from animals injected with hybridoma cells producing monomeric IgA. None of the hybridomas induced mesangial deposition when injected intraperitoneally. This animal model demonstrates the capacity of circulating IgA dimers to spontaneously form mesangial deposits and contributes to confirm the involvement of abnormalities of mucosal immunity in the pathogenesis of IgA nephropathy.
Kennel-De March
A
A
Laboratoire d'Immunologie, Faculté de Médecine and CHU de Nancy, 54500 Vandoeuvre-lès-Nancy, France.
Prin-Mathieu
C
C
Kohler
C H
CH
Kolopp-Sarda
M N
MN
Faure
G C
GC
Béné
M V
MV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D017690:Cell Transplantation; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000276:immunology* / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000378:metabolism*; D006825:Hybridomas / Q000276:immunology / Q000637:transplantation*; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism*; D008208:Lymphatic System / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014066:Palatine Tonsil / Q000276:immunology / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology
D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D016201:Receptors, Lymphocyte Homing