Ohlander C, Perlmann H, Perlmann P
Scand J Immunol. 1982 Apr;15(4):409-17. doi: 10.1111/j.1365-3083.1982.tb00665.x.
IgM antibodies, by themselves unable to induce human K-cell-mediated cytotoxicity, enhanced the lysis of TNP-coated bovine erythrocytes (TNP-Eb) induced by suboptimal concentrations of IgG antibodies. The antibodies used were directed against either TNP or intrinsic Eb antigens. The best enhancement of antibody-dependent cell-mediated cytotoxicity (ADCC) was obtained when IgG and IgM antibodies had different specificities. IgM antibodies with specificity similar to that of the IgG antibodies often inhibited rather than enhanced cytolysis. By using 125I-labelled anti-DNP IgG, the number of IgG/TNP-Eb was determined. Under the present conditions, at least 9000 IgG molecules/TNP-Eb were required for K-cell-mediated lysis in the absence of IgM. In the presence of IgM antibody concentrations optimal for enhancement of ADCC, the minimal number of IgG molecules required for induction of ADCC was 30-100 times lower. No enhancement of cytotoxicity was seen with more than the optimal concentration of IgM even when IgG binding to the target cells was not reduced by IgM. This suggested that induction of ADCC was dependent on contiguous IgG-Fc receptor interactions, which were inhibited owing to steric hindrance by excessive amounts of IgM in the critical contact areas between effector cells and target cells.
IgM抗体本身无法诱导人K细胞介导的细胞毒性，但能增强次优浓度IgG抗体诱导的三硝基苯（TNP）包被的牛红细胞（TNP-Eb）的裂解。所用抗体针对TNP或内在的Eb抗原。当IgG和IgM抗体具有不同特异性时，可获得最佳的抗体依赖性细胞介导的细胞毒性（ADCC）增强效果。与IgG抗体特异性相似的IgM抗体通常会抑制而非增强细胞溶解。通过使用125I标记的抗DNP IgG，测定了IgG/TNP-Eb的数量。在当前条件下，在没有IgM的情况下，K细胞介导的裂解至少需要9000个IgG分子/TNP-Eb。在存在对增强ADCC最佳的IgM抗体浓度时，诱导ADCC所需的IgG分子的最小数量降低了30至100倍。即使IgM不降低IgG与靶细胞的结合，超过最佳浓度的IgM也未观察到细胞毒性增强。这表明ADCC的诱导依赖于相邻的IgG-Fc受体相互作用，在效应细胞和靶细胞之间的关键接触区域中，过量的IgM由于空间位阻而抑制了这种相互作用。
