The kinetics of [3H]-dsDNA/anti-DNA immune complex formation, binding by red blood cells, and release into serum: effect of DNA molecular weight and conditions of antibody excess.
[3H]dsDNA/anti-DNA immune complexes (IC) formed, fixed complement, and bound rapidly to red blood cells (RBC) in whole blood (less than 5 min), but were released from the cells more slowly. The rate of release was dependent on both the antibody:DNA ratio and the m.w. of the DNA in the complex. For example, complexes formed with high m.w. DNA (6 X 10(6) daltons) were released more slowly (t1/2 = 60 min) than complexes formed with lower m.w. DNA (2 to 6 X 10(5) daltons, t1/2 = 15 to 20 min). The [3H]dsDNA/anti-DNA complexes, which were released from the cells as intact antigen/antibody/complement complexes, did not rebind to RBC, but did bind to Raji cells and could be precipitated by monoclonal antibody to C3d. When these released IC (RIC) containing high m.w. DNA were incubated with additional anti-DNA antibody and fresh complement, they rebound to RBC. However, RIC containing lower m.w. DNA (5 X 10(5) daltons) did not rebind to RBC under the same conditions. These data suggest that IC containing high m.w. DNA bind to and remain bound to RBC more effectively than IC containing lower m.w. DNA, and thus may be more easily cleared from the circulation by the RBC IC clearance mechanism. Thus, the size of the DNA in the IC may be a significant factor in the pathogenicity of DNA/anti-DNA complexes in SLE.
D000974:Antibodies, Antinuclear / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D000936:Antigen-Antibody Complex / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D001790:Blood Physiological Phenomena; D003165:Complement System Proteins / Q000502:physiology; D004247:DNA / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008970:Molecular Weight; D011971:Receptors, Immunologic / Q000032:analysis*
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D011971:Receptors, Immunologic; D003165:Complement System Proteins; D004247:DNA