The molecular basis of self-association of IgG-Rheumatoid factors.
The molecular basis of self-association of IgG-Rheumatoid factors.
复制标题
IgG-类风湿因子自关联的分子基础。
作者：
R. Pope;D. Teller;M. Mannik
本文从3例类风湿关节炎患者血浆中分离分离出正常血清19S ~ 6.6S组分的中间复合物。采用顺序凝胶过滤和琼脂糖抗体免疫吸附剂去除污染物来纯化这些复合物。从3例患者中分离到的复合体由带有k和λ轻链的IgG组成。沉降平衡超离心实验表明，分离的配合物具有浓度依赖的自缔合作用，其中可检测到的最小分子种分子量为292,000。这些IgG二聚体是由IgG-类风湿因子的自结合形成的，因为几乎所有由胃蛋白酶消化分离的复合物制备的F（ab）片段都与正常的IgG结合。正常IgG与F（ab）片段的一个结合位点相互作用的结合常数约为10-5升/摩尔。由于认为在两种igg -类风湿因子的自结合中形成具有两个抗原-抗体键的环状结构，因此计算二聚体形成的结合常数为10-10升/摩尔。当单体正常人IgG复合物在过量正常IgG存在下解离和重组时，不能取代IgG-类风湿因子，这一观察结果支持了IgG-类风湿因子的优先自我关联。igg -类风湿因子的自我关联可能是类风湿关节炎的普遍现象，正如其他研究者的观察结果所表明的那样。
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.