Further evidence for the antibody nature of C3 nephritic factor (C3NeF).
C3 nephritic factor (C3NeF), found in the sera of some patients with membranoproliferative glomerulonephritis, has been shown to be composed of two heavy and two light chains, like IgG; in addition it shares antigenic determinants with IgG. Purified C3NeF binds to the amplification convertase of complement, C3b,Bb, and thereby prevents decay of its C3-cleaving potential. The capability of C3NeF to bind to C3b,Bb was used as a means for purifying C3NeF to homogeneity. The investigation described in this report suggests that binding of C3NeF to C3b,Bb occurs via the Fab portion of the molecule. Pepsin treatment of eight C3NeF preparations resulted in an average loss of 76% of C3NeF functional activity. Papain treatment induced a loss of approximately 90%. The decrease in functional activity could be attributed to the accelerated rate of dissociation of 125I-F(ab')2 and 125I-Fab fragments from stabilized cell-bound C3b,Bb. The dissociation rate of 125I-F(ab')2 from C3b,Bb was comparable with the decay of the functional activity of C3b,Bb stabilized by F(ab')2 or Fab fragments of C3NeF. Although these results suggest that the stabilizing activity of C3NeF is mediated by the Fab portion of the molecule, it was found that the Fc portion also contributes to its functional activity.
D000906:Antibodies; D001665:Binding Sites; D003178:Complement C3 Nephritic Factor / Q000276:immunology*; D050577:Complement C3-C5 Convertases / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D010206:Papain / Q000494:pharmacology; D010434:Pepsin A / Q000494:pharmacology
D000906:Antibodies; D003178:Complement C3 Nephritic Factor; D003169:Complement Inactivator Proteins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D050577:Complement C3-C5 Convertases; D010206:Papain; D010434:Pepsin A