Genetic analysis of anti-TBM disease in the Norway rat.
The anti-tubular basement membrane (TBM) disease was found in own kidneys of BN, but not BN.1B rats, after immunization with BP.1N (or BP) allogeneic kidney homogenate in CFA. Both humoral [anti-TBM reaction assessed by direct immunofluorescence (IF)] and cellular response to TBM antigen (tubulointerstitial nephritis and giant cell infiltration) appeared to be controlled by an MHC-linked Ir gene(s). In the present experiments all of the 54 RT1b/RT1n heterozygous Bc rats (BN.1B x BN) x BN.1B were found to be anti-TBM positive by direct IF following the immunization mentioned above, as were all (BN.1B x BN)F1 hybrids. Among 51 RT1b/RT1b Bc homozygotes, 5 animals formed linear anti-TBM deposition in their own kidneys. The direct IF staining was somewhat weaker than in the preceding groups but continuous. However, circulating anti-TBM antibodies were not proven by indirect IF in these rats. BN animals failed to develop anti-TBM disease not only after syngeneic immunization but also after BN.1B inoculum differing in RT1 antigens alone. Only donor-recipient strain combinations involving non-RT1 differences (BP or BP.1N to BN, BN.1B or BN to BP.1N) were susceptible to the anti-TBM response. Thus the previously revealed adjuvant effect of non-RT1 alloantigenic differences was confirmed, whereas RT1 difference had no such effect nor was involved in it. In conclusion, the main anti-TBM Ir gene seems to be closely linked with, or even included in, the RT1n haplotype in our system of congenic strains. An alternative hypothesis is that there may be two separately functioning Ir genes, one within the RT1n allele and the other in linkage with RT1.
D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II; D008040:Genetic Linkage; D005838:Genotype; D006579:Heterozygote; D007114:Immunization; D007674:Kidney Diseases / Q000235:genetics* / Q000276:immunology; D007684:Kidney Tubules / Q000276:immunology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN / Q000235:genetics*; D011919:Rats, Inbred Strains / Q000235:genetics*