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Stabilization of homologous and heterologous cell-bound amplification convertases, C3bBb, by C3 nephritic factor.

1981; National Institutes of Health; Volume: 43; Issue: 1 Linguagem: Inglês

Mohamed R. Daha, Leendert A. van Es,

Renal Diseases and Glomerulopathies

C3 nephritic factor (C3NeF) may be found in the sera of patients with membranoproliferative glomerulonephritis or partial lipodystrophy. It is capable of activating the alternative pathway in normal human serum; purified C3NeF has been shown to bind to the amplification convertase of complement, C3bBb. The binding of C3NeF to C3bBb results in stabilization of the otherwise labile C3 convertase. Decay of the convertase is accompanied by release of Bi and C3NeF from C3b. To determine whether stabilization of C3bBb occurs by the binding of C3NeF to C3bBb itself, to C3b or Bb alone, homologous and heterologous cell-bound convertases were prepared with C3hu, Bhu, C3rat and Brat and exposed to C3NeF or properdin. It was found that properdin induced stabilization of C3bhuBbhu, C3bratBbhu, C3bhuBbrat and C3bratBbrat in a dose-dependent manner. On the other hand, nine out of ten C3NeF preparations were only capable of stabilizing C3bhuBbhu and C3bratBbhu and not C3bhuBbrat and C3bratBbrat. To determine whether binding of [125I]-C3NeF to the various convertases occurred, cell-bound convertase were prepared in the presence of excess Bhu and Brat, washed and further incubated with [125I]-C3NeF; the cells were then washed and the amount of cell-bound [125I]-C3NeF was measured. As in the stabilization experiments C3NeF bound only to C3huBbhu and C3bratBbhu. The binding of C3NeF was always directly related to the presence of Bbhu in the convertase. The results obtained with nine out of ten C3NeF preparations suggest that C3NeF is an autoantibody directed against antigenic determinants on Bbhu, which are exposed after interaction of Bbhu with C3bhu or C3brat. One out of ten C3NeF preparations showed reactivity with both cell-bound C3b alone and cell-bound C3bBb. These reactivities could be separated by absorption with cell-bound C3bhu.