Kuraya M, Yefenof E, Klein G, Klein E
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Eur J Immunol. 1992 Jul;22(7):1871-6. doi: 10.1002/eji.1830220729.
On a panel of nine human B cell lines we showed that the expression of the complement regulatory factors complement receptor type 2 (CR2; CD21), decay-accelerating factor, (DAF; CD55) and homologous restriction factor (HRF20, CD59) is not correlated. All lines expressed DAF, six lines carried detectable amounts of CR2 and three carried HRF20. Upon incubation in human serum, under conditions which allowed the activation of complement through the alternative pathway, the CR2-carrying lines bound C3 fragments and two of them (Ramos and one of its two sublines) were damaged. These two lines had the lowest DAF expression, less than 50% of the cells reacted with the IA10 monoclonal antibody. By modulating the expression of the complement regulatory molecules, the lytic sensitivity of the B cell lines could be altered. Blockade of DAF on the HRF20-, CR2+ lines with the specific monoclonal antibodies increased their sensitivity to lysis by human serum. With the DAF- and HRF20+ cells significant lytic effect was obtained only when they were pretreated with both of the specific antibodies. Interferon-gamma or tumor necrosis factor-alpha treatment elevated the amount of CR2 on the low-CR2 expressor line (Ramos/HR1K) which thereafter bound higher amounts of C3 fragments and was lysed when incubated in human serum. This line had relatively low DAF level and lacked HRF20. The cytokine treatment did not alter the expression of these molecules. The CR2+ Ramos and the CR2- Rael cells were treated with 5-azacytidine which induced HRF20 and increased DAF expression. In parallel with this change Ramos cells became resistant to C-mediated lysis. The experiments with the panel of human B cell lines showed thus that cytolysis through activation of complement in homologous serum can be regulated at several steps by cell surface molecules. While expression of CR2 was required for C3 fixation, DAF and HRF20 inhibited lysis. By independent modulation of the quantities of these molecules, cells acquired or lost their sensitivity.
在一组9种人B细胞系中，我们发现补体调节因子2型补体受体（CR2；CD21）、衰变加速因子（DAF；CD55）和同源限制因子（HRF20，CD59）的表达不相关。所有细胞系均表达DAF，6个细胞系携带可检测量的CR2，3个携带HRF20。在人血清中孵育时，在允许通过替代途径激活补体的条件下，携带CR2的细胞系结合C3片段，其中两个（拉莫斯细胞系及其两个亚系之一）受损。这两个细胞系的DAF表达最低，不到50%的细胞与IA10单克隆抗体反应。通过调节补体调节分子的表达，可以改变B细胞系的溶解敏感性。用特异性单克隆抗体阻断HRF20、CR2+细胞系上的DAF可增加其对人血清裂解的敏感性。对于DAF+和HRF20+细胞，只有在用两种特异性抗体预处理后才获得显著的裂解效果。干扰素-γ或肿瘤坏死因子-α处理可提高低CR2表达细胞系（拉莫斯/HR1K）上CR2的量，此后该细胞系结合更多的C3片段，并在人血清中孵育时被裂解。该细胞系的DAF水平相对较低且缺乏HRF20。细胞因子处理未改变这些分子的表达。用5-氮杂胞苷处理CR2+拉莫斯细胞系和CR2-雷尔细胞系，可诱导HRF20并增加DAF表达。随着这种变化，拉莫斯细胞对C介导的裂解产生抗性。因此，用人B细胞系进行的实验表明，同源血清中补体激活引起的细胞溶解可在多个步骤由细胞表面分子调节。虽然C3固定需要CR2的表达，但DAF和HRF20可抑制细胞溶解。通过独立调节这些分子的量，细胞获得或丧失其敏感性。
