QUANTITATIVE STUDIES OF IMMUNOGLOBULIN DEPOSITION IN KIDNEY, GLOMERULAR CELL-PROLIFERATION AND GLOMERULOSCLEROSIS IN NZB-NZW F1 HYBRID MICE

  • 1 January 1977
    • journal article
    • research article
    • Vol. 27  (2) , 261-268
Abstract
Using the NZB and NZB/NZW F1 (B/W) hybrid mouse as a model for systemic lupus erythematosus, an effort was made to quantitate immune complex deposition in the glomeruli by immunofluorescent staining of immunoglobulin, glomerular cellular proliferation by radioautographic measurement of [3H]Tdr [thymidine] incorporation into the glomerular cells in vivo, and glomerular scarring by PAS [periodic acid-Schiff] staining. The relationship between these changes and increasing age was examined. Dividing glomerular cells were labeled in vivo after injection of [3H]Tdr. This provided a reproducible measure of the proliferative process in the nephritis of B/W mice. In C57Bl/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. 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 mo. of age and reaching a peak at 9 mo. Increase in glomerular cell proliferation began about 2 mo. after the onset of immune complex deposition but also reached a maximum at 9 mo. Glomerular sclerosis was the last change to appear and continued after the other 2 parameters measured had begun to decline. 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 analyzing the differential effects of various types of treatment of immune complex nephritis in animals.