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Clin Exp Immunol. Feb 1977; 27(2): 261–268.
PMCID: PMC1540778

Quantitative studies of immunoglobulin deposition in the kidney, glomerular cell proliferation and glomerulosclerosis in NZB/NZW F1 hybrid mice.

Abstract

Using the NZB and NZB/NZW F1 (B/W) hybrid mouse as a model for systemic lupus erythematosus, an effort has been made to quantitate: (1) immune complex deposition in the glomeruli by immunofluorescent staining of immunoglobulin, (2) glomerular cellular proliferation by radioautographic measurement of [3H]Tdr incorporation into the glomerular cells in vivo, and (3) glomerular scarring by PAS staining. The relationship between these changes and increasing age has been examined. By radioautography it was observed that dividing glomerular cells were labelled in vivo after injection of [3H]Tdr. This provided a reproducible measure of the proliferative process in the nephritis of B/W mice. In C57B1/6J and CBA/J mice, which have a low incidence of glomerular disease, little change in the amount of glomerular cell proliferation was observed with increasing age. The NZB strain of animals showed a somewhat increased level of proliferation but this did not increase with age. In striking contrast, glomerular cell proliferation in the B/W mice increased rapidly with age. The earliest change observed in the kidney was the deposition of immunofluorescent material in the mesangium and glomerular capillary basement membrane beginning between 3 and 5 months of age and reaching a peak at 9 months. Increase in glomerular cell proliferation began about 2 months after the onset of immune complex deposition but also reached a maximum at 7 months. Glomerular sclerosis was the last change to appear and continued after the other two parameters measured has begun to decline. These data suggest that the deposition of immune complexes in the glomerulus may be an important triggering mechanism for renal cell proliferation and glomerulosclerosis in the B/W mouse. The techniques described would provide a sensitive and reproducible quantitative method for analysing the differential effects of various types of treatment of immune complex nephritis in animals.

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Selected References

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  • Asko-Seljavaara S. Kidney tubular cell proliferation in burned mice. Scand J Plast Reconstr Surg. 1975;9(1):25–30. [PubMed]
  • Clarkson AR, MacDonald MK, Petrie JJ, Cash JD, Robson JS. Serum and urinary fibrin-fibrinogen degradation products in glomerulonephritis. Br Med J. 1971 Aug;3(5772):447–451. [PMC free article] [PubMed]
  • Comerford FR, Cohen AS, Desai RG. The evolution of the glomerular lesion in NZB mice. A light and electron microscopic study. Lab Invest. 1968 Dec;19(6):643–651. [PubMed]
  • Croker BP, Jr, del Villano BC, Jensen FC, Lerner RA, Dixon FJ. Immunopathogenicity and oncogenicity of murine leukemia viruses. I. Induction of immunologic disease and lymphoma in (BALB-c times NZB)F1 mice by Scripps leukemia virus. J Exp Med. 1974 Oct 1;140(4):1028–1048. [PMC free article] [PubMed]
  • GERMUTH FG., Jr A comparative histologic and immunologic study in rabbits of induced hypersensitivity of the serum sickness type. J Exp Med. 1953 Feb 1;97(2):257–282. [PMC free article] [PubMed]
  • Gershwin ME, Steinberg AD. Qualitative characteristics of anti-DNA antibodies in lupus nephritis. Arthritis Rheum. 1974 Nov-Dec;17(6):947–954. [PubMed]
  • Gilliam JN, Hurd ER, Ziff M. Subepidermal deposition of immunoglobulin in NZB/NZW F hybrid mice. J Immunol. 1975 Jan;114(1 Pt 1):133–137. [PubMed]
  • Hattori T. On cell proliferation and differentiation of the fundic mucosa of the golden hamster. Fractographic study combined with microscopy and 3H-thymidine autoradiography. Cell Tissue Res. 1974 Apr 11;148(2):213–226. [PubMed]
  • HELYER BJ, HOWIE JB. Renal disease associated with positive lupus erythematosus tests in a cross-bred strain of mice. Nature. 1963 Jan 12;197:197–197. [PubMed]
  • HOLMES MC, BURNET FM. THE NATURAL HISTORY OF AUTOIMMUNE DISEASE IN NZB MICE. A COMPARISON WITH THE PATTERN OF HUMAN AUTOIMMUNE MANIFESTATIONS. Ann Intern Med. 1963 Sep;59:265–276. [PubMed]
  • HUNT TE, HUNT EA. Radioautographic study of proliferation in the stomach of the rat using thymidine-H3 and compound 48/80. Anat Rec. 1962 Apr;142:505–517. [PubMed]
  • Karnovsky MJ, Ainsworth SK. The structural basis of glomerular filtration. Adv Nephrol Necker Hosp. 1972;2:35–60. [PubMed]
  • LACHMANN PJ, MULLER-EBERHARD HJ, KUNKEL HG, PARONETTO F. The localization of in vivo bound complement in tissue section. J Exp Med. 1962 Jan 1;115:63–82. [PMC free article] [PubMed]
  • Lambert PH, Dixon FJ. Genesis of antinuclear antibody in NZB-W mice: role of genetic factors and of viral infections. Clin Exp Immunol. 1970 Jun;6(6):829–839. [PMC free article] [PubMed]
  • Lampert PW, Oldstone MB. Host immunoglobulin G and complement deposits in the choroid plexus during spontaneous immune complex disease. Science. 1973 Apr 27;180(4084):408–410. [PubMed]
  • Lerner RA, Jensen F, Kennel SJ, Dixon FJ, Des Roches G, Francke U. Karyotypic, virologic, and immunologic analyses of two continuous lymphocyte lines established from New Zealand black mice: possible relationship of chromosomal mosaicism to autoimmunity. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2965–2969. [PMC free article] [PubMed]
  • MCCLUSKEY RT, BENACERRAF B, POTTER JL, MILLER F. The pathologic effects of intravenously administered soluble antigen-antibody complexes. I. Passive serum sickness in mice. J Exp Med. 1960 Feb 1;111:181–194. [PMC free article] [PubMed]
  • MELLORS RC. AUTOIMMUNE DISEASE IN NZB/BL MICE. I. PATHOLOGY AND PATHOGENESIS OF A MODEL SYSTEM OF SPONTANEOUS GLOMERULONEPHRITIS. J Exp Med. 1965 Jul 1;122:25–40. [PMC free article] [PubMed]
  • Mellors RC, Aoki T, Huebner RJ. Further implication of murine leukemia-like virs in the disorders of NZB mice. J Exp Med. 1969 May 1;129(5):1045–1062. [PMC free article] [PubMed]
  • MELLORS RC, ORTEGA LG, HOLMAN HR. Role of gamma globulins in pathogenesis of renal lesions in systemic lupus erythematosus and chronic membranous glomerulonephritis, with an observation on the lupus erythematosus cell reaction. J Exp Med. 1957 Aug 1;106(2):191–202. [PMC free article] [PubMed]
  • MESSIER B, LEBLOND CP. Cell proliferation and migration as revealed by radioautography after injection of thymidine-H3 into male rats and mice. Am J Anat. 1960 May;106:247–285. [PubMed]
  • Miyasato F, Manaligod JR, Pollak VE. Auto-immune disease in NZB and NZB-NZW F1 mice. Natural history and pathology. Arch Pathol. 1967 Jan;83(1):20–30. [PubMed]
  • Shirai T, Yoshiki T, Mellors RC. Age-decrease of cells sensitive to an autoantibody-specific for thymocytes and thymus-dependent lymphocytes in NZB mice. Clin Exp Immunol. 1972 Dec;12(4):455–464. [PMC free article] [PubMed]
  • Steinberg AD, Pincus T, Talal N. The pathogenesis of autoimmunity in New Zealand mice. 3. Factors influencing the formation of anti-nucleic acid antibodies. Immunology. 1971 Apr;20(4):523–531. [PMC free article] [PubMed]
  • Stutman O. Lymphocyte subpopulations in NZB mice: deficit of thymus-dependent lymphocytes. J Immunol. 1972 Sep;109(3):602–611. [PubMed]
  • Teague PO, Yunis EJ, Rodey G, Fish AJ, Stutman O, Good RA. Autoimmune phenomena and renal disease in mice. Role of thymectomy, aging, and involution of immunologic capacity. Lab Invest. 1970 Feb;22(2):121–130. [PubMed]
  • VASSALLI P, MCCLUSKEY RT. THE PATHOGENIC ROLE OF FIBRIN DEPOSITION IN IMMUNOLOGICALLY INDUCED GLOMERULONEPHRITIS. Ann N Y Acad Sci. 1964 Aug 27;116:1052–1062. [PubMed]
  • VASSALLI P, SIMON G, ROUILLER C. ELECTRON MICROSCOPIC STUDY OF GLOMERULAR LESIONS RESULTING FROM INTRAVASCULAR FIBRIN FORMATION. Am J Pathol. 1963 Oct;43:579–617. [PMC free article] [PubMed]
  • Yoshiki T, Mellors RC, Strand M, August JT. The viral envelope glycoprotein of murine leukemia virus and the pathogenesis of immune complex glomerulonephritis of New Zealand mice. J Exp Med. 1974 Oct 1;140(4):1011–1027. [PMC free article] [PubMed]

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