Kwekkeboom J, De Boer M, Tager J M, De Groot C
Laboratory of Cell Biology and Histology, University of Amsterdam, Academic Medical Center, The Netherlands.
Immunology. 1993 Jul;79(3):439-44.
A mutant subclone of the murine thymoma EL-4, known as EL4B5, can strongly activate human B cells to proliferate and differentiate in a cell-cell contact-dependent manner. We have investigated whether interaction via CD40 plays a role in this helper activity. For this purpose, three newly generated anti-CD40 monoclonal antibodies (mAb) were used. In contrast with other anti-CD40 mAb described in the literature, these mAb did not co-stimulate proliferation of human B cells. On the other hand, these novel mAb could inhibit the co-stimulatory effect of the previously described anti-CD40 mAb S2C6 on anti-IgM-induced human B-cell proliferation. It was found that addition of these non-stimulatory anti-CD40 mAb could completely inhibit EL4B5-induced human B-cell proliferation. Maximal inhibition occurred already at a mAb concentration of 10 ng/ml. Similarly, a fusion protein, consisting of the extracellular portion of CD40 and human IgM constant domains CH2, CH3 and CH4, could completely inhibit EL4B5-induced human B-cell proliferation. Induction of human B-cell proliferation by EL4B5 cells was also inhibited by anti-CD40 mAb S2C6 and G28.5, but less effectively. In contrast, mAb against B-cell surface antigens CD20 or B7 had no inhibitory effects. It is concluded that interaction via CD40 is essential for the induction of human B-cell proliferation by EL4B5 cells.
小鼠胸腺瘤EL-4的一个突变亚克隆，即EL4B5，能够以细胞间接触依赖的方式强烈激活人B细胞增殖和分化。我们研究了通过CD40的相互作用是否在这种辅助活性中发挥作用。为此，使用了三种新产生的抗CD40单克隆抗体（mAb）。与文献中描述的其他抗CD40 mAb不同，这些mAb不会共刺激人B细胞增殖。另一方面，这些新型mAb可以抑制先前描述的抗CD40 mAb S2C6对抗IgM诱导的人B细胞增殖的共刺激作用。发现添加这些无刺激作用的抗CD40 mAb可以完全抑制EL4B5诱导的人B细胞增殖。在mAb浓度为10 ng/ml时就已经出现最大抑制作用。同样，一种由CD40的细胞外部分与人IgM恒定结构域CH2、CH3和CH4组成的融合蛋白也可以完全抑制EL4B5诱导的人B细胞增殖。抗CD40 mAb S2C6和G28.5也能抑制EL4B5细胞诱导的人B细胞增殖，但效果较差。相比之下，针对B细胞表面抗原CD20或B7的mAb没有抑制作用。得出的结论是，通过CD40的相互作用对于EL4B5细胞诱导人B细胞增殖至关重要。
