Susceptibility for infection-related glomerulopathy depends on non-MHC genes.
BALB/c mice infected with Trypanosoma brucei and treated seven days after inoculation with Diminazene aceturate develop polyclonal B-cell stimulation, including production of antibodies to known nephritogenic autoantigens and glomerular disease associated with severe albuminuria. To investigate if the susceptibility for glomerular disease in this model is linked to MHC or non-MHC genes, we studied this disease in six mouse strains that were partly congenic for their MHC and partly congenic for their non-MHC genes. The course of the infection was measured by parasitemia and related to (auto)antibody production, proteinuria and glomerular deposition of immunoglobulins. The mouse strains could be divided into two groups. The first group consisted of the C57BL/6 (H-2b), C57BL/10 (H-2b) and B10.D2 (H-2d) strains, which proved to be relatively resistant to infection with Trypanosoma brucei (that is, spontaneous survival > 25 days). In sera of these mice antibodies to a broad range of antigens could be found 14 days after inoculation; no proteinuria was observed. The second group consisted of the BALB/c (H-2d), BALB.B (H-2b) and DBA/2 (H-2d) strains, which were relatively susceptible to the infection. In these animals proteinuria occurred and a broad polyclonal B-cell stimulation was seen 42 days after inoculation. No correlation was found between the specificity of circulating antibodies and the occurrence of proteinuria or a glomerular fluorescence pattern. These results indicate that in this model non-MHC genes govern the outcome of the infection as well as the development of polyclonal B-cell stimulation and proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
van Velthuysen
M L
ML
Laboratory for Pathology, University of Leiden, The Netherlands.
Veninga
A
A
Bruijn
J A
JA
de Heer
E
E
Fleuren
G J
GJ
D000419:Albuminuria / Q000235:genetics; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D005921:Glomerulonephritis / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000235:genetics* / Q000276:immunology