Kinetics of circulating immune complex formation during the induction of chronic serum sickness in rats

To study the mechanism of the induction of nephritis, chronic serum sickness (CSS) was induced in Fisher rats and the kinetics of immune complex formation and immunohistological glomerular alterations were studied up to the 13th week following pre-immunization with bovine serum albumin (BSA). Serum circulating immune complexes (CIC) were detectable in high titer from the 8th week (intravenous stage). After immunization with BSA, serum anti-BSA antibodies increased gradually and remained high in titer even after injection of BSA. At the 9th week, BSA, IgG and C3 were detectable transiently by immunofluorescence in glomerular capillary lumens. Light and electron microscopic findings were normal. At the 12th week, BSA, IgG and C3 were observed by immunofluorescence in glomerular basement membrane and increased in intensity with time. Urinary protein excretion was detected at the 11th week and the amount excreted increased with time. In conclusion, the change in antibody titer and CIC level indicated a smaller amount of antigens than antibodies during the induction of nephritis and CIC seemed to be formed in antibody excess. In addition, there was a time-lag of several weeks between the onset of nephritis (the onset of proteinuria and the deposition of IC in a glomerulus) and the rise of the CIC titer. The continuation of the high CIC titer and the saturation of the reticuloendothelial system seemed to be necessary to induce CSS nephritis in rats.