C4-mediated inhibition of immune precipitation and differences in inhibitory action of genetic variants, C4A3 and C4B1.
The inhibition of immune precipitation is mediated by the classical complement pathway. We report here that the rate of precipitate formation depends on the genetic form of human C4 present during immune precipitation. C4A3 is more effective than C4B1 in its capacity to inhibit the rate of immune precipitate formation in serum and in serum-free reaction mixtures containing C1 and C4. Immune precipitates form within seconds after antigen is mixed with antibody, and the activation of the classical pathway is known to occur within seconds after C1 binds to antibody molecules. The covalent deposition of C4b on immune complexes is an essential step in the inhibition of immune precipitate formation, and if any of the reactions that lead to covalent C4b deposition become limiting, the rate of immune precipitation could exceed the complement system's inhibitory capacity. Hence, the inhibition of this rate may be an important function underlying the complement-mediated processing of immune complexes, and a decreased ability of the complement system to mediate this process in the presence of C4B1, in contrast to C4A3, could explain, at least in part, the association between the C4A-null phenotype and autoimmune diseases such as systemic lupus erythematosus.
Paul
L
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James S. McDonnell Department of Genetics, Washington University School of Medicine, St. Louis, Mo.
Skanes
V M
VM
Mayden
J
J
Levine
R P
RP
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D003167:Complement Activation; D003181:Complement C4 / Q000235:genetics*; D006168:Guinea Pigs; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009391:Nephelometry and Turbidimetry; D011233:Precipitin Tests; D012710:Serum Albumin, Bovine / Q000276:immunology
D000936:Antigen-Antibody Complex; D003181:Complement C4; D007074:Immunoglobulin G; D012710:Serum Albumin, Bovine