The molecular basis of self-association of IgG-Rheumatoid factors.
The intermediate complexes, sedimenting between 19S and 6.6S components of normal serum on analytical ultracentrifugation, were purified from plasma of three patients with rheumatoid arthritis. Sequential gel filtration and removal of contaminants by agarose-antibody immunoadsorbents were employed for purification of these complexes. The isolated complexes from the three patients consisted of IgG with k and lambda light chains. Sedimentation equilibrium ultracentrifugation experiments showed that the isolated complexes underwent concentration-dependent self-association, whereby the  smallest detectable molecular species had a molecular weight of 292,000. These IgG dimers were formed by  self-association of IgG-rheumatoid factors, since nearly all F(ab) fragments, prepared from the isolated complexes by  pepsin digestion, bound to normal IgG. The association constants for the interaction between normal IgG and one binding site of the F(ab) fragments were about 10-5 liters/mole. Since a cyclic structure with two antigen-antibody bonds was thought to form in the self-association of two IgG-rheumatoid factors, the association constant for dimer formation was calculated to be 10-10 liters/mole. The preferential self-association of IgG-rheumatoid factor was supported by the observation that monomeric normal human IgG did not replace the IgG-rheumatoid factor when the complexes were dissociated and reformed in the presence of excess normal IgG. The self-association of IgG-rheumatoid factors may be a general phenomenon in rheumatoid arthritis, as suggested by the observations of other investigators.
D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002499:Centrifugation, Density Gradient; D002850:Chromatography, Gel; D006801:Humans; D005779:Immunodiffusion; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D008970:Molecular Weight; D010434:Pepsin A; D012217:Rheumatoid Factor; D013395:Sucrose; D014462:Ultrafiltration
D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D013395:Sucrose; D012217:Rheumatoid Factor; D010434:Pepsin A