Production of IgG and IgM autoantibody to the alternative pathway C3 convertase in normal individuals and patients with membranoproliferative glomerulonephritis.
To understand the origin of autoantibody production, we studied the ontogeny of antibody to the alternative pathway C3 convertase (C3 nephritic factor or C3NeF). Peripheral blood mononuclear cells from newborns, normal adults, and patients with membranoproliferative glomerulonephritis produced IgM and IgG C3NeF after culture for 14 days with pokeweed mitogen. Both IgM and IgG moieties appear to have the same paratope and are able to inhibit each other's binding and function. The affinity constant for each of the C3NeF molecules was moderately high (10(8) liters/mol) and there appeared to be little difference between the Ka values for the IgG and the IgM autoantibodies or between Ka values for autoantibodies isolated from newborns, adults, and patients. These data, then, indicate that the ability to produce C3NeF autoantibody is present from the time of birth in normal individuals. The high affinity of these autoantibodies under normal conditions suggests that C3NeF may play a more important physiological role than previously anticipated.
Spitzer
R E
RE
Department of Pediatrics, Health Science Center, State University of New York, Syracuse 13210.
Stitzel
A E
AE
Tsokos
G C
GC
D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology*; D003178:Complement C3 Nephritic Factor / Q000276:immunology*; D050577:Complement C3-C5 Convertases / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000276:immunology*; D003170:Complement Pathway, Alternative; D000939:Epitopes; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D003178:Complement C3 Nephritic Factor; D003169:Complement Inactivator Proteins; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D050577:Complement C3-C5 Convertases