C3 nephritic factor protects bound C3bBb from cleavage by factor I and human erythrocytes.
C3 nephritic factor is an autoantibody to the alternative-pathway C3 convertase (C3bBb) which increases the half-life of the convertase both in the presence and absence of serum regulatory proteins. Human erythrocytes contain membrane proteins which also can regulate C3bBb. One of these proteins, the C3b/C4b receptor (CR1), plays an important role in the processing of soluble immune complexes. C3b which is fixed to immune complexes binds to CR1 and is cleaved by factor I to C3c and C3dg. We have tested the effectiveness of the nephritic factor in protecting bound C3b from cleavage by factor I and human erythrocytes. Sheep erythrocyte intermediates EAC1423b were prepared using 125I-labeled C3 and incubated with factors B and D in the presence and absence of nephritic factor. Breakdown of C3b was measured by release of 125I-C3c following incubation with human erythrocytes and factor I. Purified IgG from two patients with nephritic factor prevented C3c release in a dose-dependent manner. Normal human IgG was ineffective as was nephritic factor in the absence of factor B. Factor P also inhibited the release of C3c in the presence of factor B with equivalent activity at approx. 20-fold higher concns than nephritic factor. These results indicate that nephritic factor can impair human erythrocyte dependent degradation of C3b in alternative-pathway-activating immune complexes.
D003166:Complement Activating Enzymes / Q000378:metabolism*; D003178:Complement C3 Nephritic Factor / Q000502:physiology*; D050577:Complement C3-C5 Convertases / Q000378:metabolism*; D011415:Complement Factor B / Q000502:physiology; D003169:Complement Inactivator Proteins / Q000502:physiology*; D003170:Complement Pathway, Alternative; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000276:immunology*; D005340:Fibrinogen / Q000502:physiology*; D006801:Humans
D003178:Complement C3 Nephritic Factor; D003169:Complement Inactivator Proteins; D005340:Fibrinogen; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B