Autoimmune interstitial nephritis induced in inbred mice. Analysis of mouse tubular basement membrane antigen and genetic control of immune response to it.
Purified murine tubular basement membrane (TBM) antigen (molecular weight, 32,000) induced interstitial lesions in Brown Norway (BN) rats. TBM antigen prepared from mice of 3 inbred strains--BALB/c, C3H/He, and C57BL/6--and outbred ddY mice possessed both antigenicity and nephritogenecity. Using these TBM antigens, the roles of humoral and cellular immunity in the development of interstitial nephritis (IN) and the genetic control of the induction of IN in inbred mice were investigated. BALB/c mice were highly susceptible to IN and showed a high antibody response and a high lymphocyte proliferative response to syngeneic and allogeneic TBM antigen, whereas C57BL/6 mice did not. C3H/He mice, in which minimal interstitial lesions developed, showed a high antibody response but a low proliferative response of T cells to TBM antigen. TBM antigen sensitized T cells induced interstitial lesions, but anti-TBM antisera did not do so. Thus, the development of IN seemed to be related closely to cellular immunity. Further studies with their hybrids, backcrosses, congenic mice, and recombinant mice suggested that the induction of IN and the immune response to TBM antigen are controlled by 1 or a few dominant genes, whose loci are within, or closely linked to, the H-2 complex.
Ueda
S
S
First Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Wakashin
M
M
Wakashin
Y
Y
Yoshida
H
H
Azemoto
R
R
Iesato
K
K
Mori
T
T
Mori
Y
Y
Ogawa
M
M
Okuda
K
K
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology*; D002455:Cell Division; D003433:Crosses, Genetic; D006824:Hybridization, Genetic; D007116:Immunization, Passive; D007668:Kidney / Q000276:immunology; D007684:Kidney Tubules / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D009395:Nephritis, Interstitial / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000473:pathology
D000906:Antibodies; D000941:Antigens