title: Experimental lupus nephritis in severe combined immunodeficient (SCID) mice: remodelling of the glomerular lesions by bystander IgM antibodies.
abstract: MRL/Mp-lpr/lpr (MRL/lpr) mice develop glomerular lesions with regular variations in their histopathological manifestations, similar to those in lupus nephritis. These lesions are mainly either cell-proliferative or wire loop-like and are associated with glomerular deposits of immunoglobulins, most frequently IgG and IgM. We previously established a nephritogenic IgG3-producing hybridoma clone, B1, from an MRL/lpr mouse, which induces only a 'wire loop-like' type of glomerular lesion when injected into SCID mice. Injection of SCID mice with an anti-trinitrophenyl IgM antibody-producing hybridoma clone, Sp6, following injection of the B1 clone, however, resulted in the development of a 'cell-proliferative' type of glomerular lesion, associated with an accumulation of both antibodies in glomeruli. This accumulation occurred even though Sp6 IgM antibodies did not react with B1 IgG3 antibodies and vice versa. A mutant clone of Sp6, T/13microE/3.1, which produces antibodies deficient in C1q binding, produced a similar effect as that of the Sp6 clone, i.e. 'cell-proliferative' lesions. Again the B1 antibodies did not react with T/13microE/3. 1-IgM antibodies and vice versa. We therefore conclude that bystander IgM antibodies contribute to the remodelling of glomerular lesions in situ, following glomerular injury by the nephritogenic antibodies.
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: M R
authors.initials: MR
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Terasaki
authors.forename: E
authors.initials: E
authors.lastname: Kondo
authors.forename: H
authors.initials: H
authors.lastname: Shiwaku
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuoka
authors.forename: M
authors.initials: M
authors.lastname: Nose
mesh_terms: D000818:Animals; D001666:Binding Sites, Antibody / Q000235:genetics; D002455:Cell Division / Q000276:immunology; D015922:Complement C1q / Q000378:metabolism; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007075:Immunoglobulin M / Q000097:blood / Q000235:genetics / Q000502:physiology*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology*; D008181:Lupus Nephritis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D016513:Mice, SCID; D009154:Mutation
chemical_list: D007075:Immunoglobulin M; D015922:Complement C1q