Activated C3 (C3b) in the nephritic glomerulus

An autoradiographic technique was developed to assess in the nephritic glomerulus the relative amount of C3 which is in the activated form, C3b, compared with the inactivated form, iC3b. Frozen renal biopsy sections from children and young adults with glomerulonephritis were assessed for the C3b fraction of total C3, using a radiolabeled monoclonal anti-C3c. Grain counts with this antibody, before and after reacting the section with 0.0002% typsin, gave the relative amounts of total C3 and C3b, respectively. C3b was found in all diseases studied. To explain its presence, glomerular C3b acceptors which would restrict C3b inactivation were sought by immuno-fluorescence studies. C3b acceptor candidates were: igG in aggregated form, IgA as found in the IgA nephropathies and the C3/C5 convertase, C4b,2a,3b. In acute post-streptococcal glomerulonephritis and membranoproliferative glomerulonephritis type III, diseases in which these acceptors were lacking, it is postulated that the nephritis strain-associated protein and absence of membrane cofactor protein, respectively, may be responsible for C3b deposition. The phlogistic effect of C3b is mediated largely by one of its products, C5b-9. However, the C3b: total C3 ratio failed to correlate with indices of glomerular inflammation. probably in part because the ratio is not a measure of total glomerular C3b.