TUBULOINTERSTITIAL NEPHRITIS INDUCED BY MONOCLONAL ANTI-PROXIMAL TUBULAR BASEMENT-MEMBRANE ANTIBODIES IN MICE

Tubulointerstitial nephritis (TIN) was induced by monoclonal anti-tubular basement membrane (TBM) antibodies. Hybridomas producing anti-TBM antibodies were produced by the fusion of a mouse parental cell line with BALB/c mice which had been immunized with Wistar rat renal cortices. Three hybridoma cell lines were selected for production of antibodies against proximal TBM by indirect immunofluorescence. The isotypes of these monoclonal antibodies (MoAbs) were determined to be of the IgM class by double immunodiffusion. Subsequently, 6-week-old female BALB/c mice were injected intraperitoneally with cells (1 × 107) of anti-TBM antibody-producing hybridomas. 39-1, 39-4, or 339-3. As a control, a monoclonal IgM-producing myeloma cell line was used. Proteinuria developed from Day 8, reaching 200 to 300 mg% in mice from the experimental groups, while in the control mice, urinary protein did not exceed 50 mg%. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, the excreted urinary proteins proved to be of low molecular weight. An immunofluorescent study revealed a linear localization of IgM along the proximal TBM from Day 4, and light microscopy showed focal degenerative alteration in proximal tubules and focal round cell infiltration in the interstitium. Electron microscopy revealed dense deposits on some proximal TBM. These results indicate that monoclonal anti-TBM IgM antibodies can induce TIN as a result of persistent production of antibodies from intraperitoneally injected hybridomas. © 1990.