Bakács T, Végh Z, Merry A H, Sim R B, Varga L, Kertész Z, Tusnády G, Klein E
Department of Immunology, National Institute of Oncology, Budapest, Hungary.
Immunol Lett. 1993 Mar;35(3):219-28. doi: 10.1016/0165-2478(93)90186-6.
The lysis of group AB erythrocytes by human complement was studied by different anti-A and anti-B IgM monoclonal antibodies (mabs) in a 51Cr-release assay. The concentration of membrane-bound immunoglobulin was detected by ELISA, and the amount of C1q and C3 bound to sensitized red cells was measured by using purified, 125I-labelled molecules. We have demonstrated that there is an exponential relationship between the concentration of the sensitizing IgM mabs and C1q binding to the sensitized AB cell. The efficiency of binding was related to the number of antibodies bound; thus, anti-A sensitized cells bound 3-6 times more C1q than anti-B sensitized cells did. AB cells, on the other hand, bound similar amounts of C3 whether anti-A or anti-B was present. The lytic efficiencies of the various IgM mabs during short incubation times were different, suggesting that the complement activation rates vary widely with different antibodies on the AB cell membrane. The binding of C1q to an antibody-sensitized target activates a cascade, whose components may migrate away from the sensitizing antibody; interactions between the activation processes generated by the anti-A and anti-B antibodies may thus occur. Choosing appropriate pairs of anti-A and anti-B mabs for the simultaneous sensitization of AB cells has indeed resulted in stimulation in some and inhibition in other combinations of mabs. It is suggested that stimulation is observed when the activated intermediates are produced in excess, whereas inhibition occurs when a shortage of activated intermediates prevents mutual utilization.
在一项⁵¹Cr释放试验中,利用不同的抗A和抗B IgM单克隆抗体(mabs)研究了人补体对AB血型红细胞的溶解作用。通过酶联免疫吸附测定法(ELISA)检测膜结合免疫球蛋白的浓度,并使用纯化的¹²⁵I标记分子测量与致敏红细胞结合的C1q和C3的量。我们已经证明,致敏IgM单克隆抗体的浓度与C1q结合到致敏AB细胞之间存在指数关系。结合效率与结合的抗体数量有关;因此,抗A致敏细胞结合的C1q比抗B致敏细胞多3至6倍。另一方面,无论存在抗A还是抗B,AB细胞结合的C3量相似。在短孵育时间内,各种IgM单克隆抗体的溶解效率不同,这表明补体激活率因AB细胞膜上不同的抗体而有很大差异。C1q与抗体致敏靶标的结合激活了一个级联反应,其成分可能会从致敏抗体处迁移离开;因此,抗A和抗B抗体产生的激活过程之间可能会发生相互作用。选择合适的抗A和抗B单克隆抗体对同时致敏AB细胞,确实在某些单克隆抗体组合中产生了刺激作用,而在其他组合中则产生了抑制作用。有人认为,当激活中间体产生过量时会观察到刺激作用,而当激活中间体短缺阻止相互利用时则会发生抑制作用。