Higaki Y, Hata D, Kanazashi S, Horiguchi Y, Yamaoka K, Ohshima Y, Kim K M, Heike T, Mayumi M
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Immunol Cell Biol. 1994 Jun;72(3):205-14. doi: 10.1038/icb.1994.31.
The mechanisms involved in the inhibition of growth of a human B lymphoma cell line, B104, by anti-MHC class II antibodies (Ab) were compared with those in anti-IgM Ab-induced B104 growth inhibition. Two anti-MHC class II Ab, L227 and 2.06, inhibited the growth of B104 cells, although 2.06, but not L227, needed to be further cross-linked with a goat anti-mouse IgG Ab (GAM) to show the effect. L227 induced an increase in intracellular free Ca2+ concentration ([Ca2+]i) from the intracellular pool and little or no protein tyrosine phosphorylation, phosphatidyl inositol turnover, or expression of Egr-1 mRNA, whereas 2.06 plus GAM induced an increase in [Ca2+]i from both the intracellular and, in particular, the extracellular pools. The inhibition of B104 cell growth induced by anti-MHC class II Ab was Ca(2+)-independent and not inhibited by actinomycin D or cyclosporin A, and cell cycle arrest at the G2/M interphase was not observed. These features are very different from those observed in B104 cell death induced by anti-IgM Ab. Neither DNA fragmentation nor the morphology of apoptosis was observed. These findings demonstrate that cross-linking of MHC class II molecules transduced the negative signals through intracellular mechanisms different from those present in the cross-linking of surface IgM.
将抗MHC II类抗体（Ab）抑制人B淋巴瘤细胞系B104生长的机制与抗IgM抗体诱导的B104生长抑制机制进行了比较。两种抗MHC II类抗体L227和2.06抑制了B104细胞的生长，不过2.06需要与山羊抗小鼠IgG抗体（GAM）进一步交联才能显示出效果，而L227则不需要。L227诱导细胞内游离Ca2+浓度（[Ca2+]i）从细胞内储存库升高，且几乎没有或没有蛋白质酪氨酸磷酸化、磷脂酰肌醇周转或Egr-1 mRNA表达，而2.06加GAM则诱导[Ca2+]i从细胞内特别是细胞外储存库升高。抗MHC II类抗体诱导的B104细胞生长抑制是Ca(2+)非依赖性的，不受放线菌素D或环孢素A的抑制，且未观察到细胞周期阻滞在G2/M期。这些特征与抗IgM抗体诱导的B104细胞死亡中观察到的特征非常不同。未观察到DNA片段化或凋亡形态。这些发现表明，MHC II类分子的交联通过与表面IgM交联中不同的细胞内机制转导了负信号。
