A Novel Type of Cell Death of Lymphocytes induced by mAb

我们早些时候发现，大鼠的单抗(MAb)RE2能够以补体非依赖性的方式诱导激活的但不是静止的小鼠淋巴细胞迅速死亡，这是一种不同于典型的细胞凋亡或坏死的细胞死亡。我们在此发现，这种细胞死亡与涉及Fas、Caspase的途径无关。我们发现RE2表位位于鼠类Ia2结构域上。然而，A3结构域在传递死亡信号方面起着关键作用，它介导了MHC-I类整合素细丝系统的广泛聚集，产生了膜孔。在T细胞激活相关的暴发型肝炎小鼠模型中，给予单抗RE2几乎完全抑制了肝细胞损伤的发展。使用单抗诱导这种形式的细胞死亡可能对患有免疫性疾病的人有潜在的治疗作用。

We earlier found that a rat monoclonal antibody (mAb) RE2 can induce rapid death of murine activated, but not resting, lymphocytes in a complement independent manner, a cell death differing from typical apoptosis or necrosis. We here found that this cell death is independent of pathways involving Fas, caspase. We found that RE2 epitope resides on the murine class I a2 domain. However, the a3 domain plays a key role in transducing the death signal, which mediates extensive aggregation of the MHC class I- integrinactin filament system, giving rise to membrane pores. In mouse models with T cell activation- associated fulminant hepatitis, administration of mAb RE2 almost completely inhibited the development of liver cell injuries. Induction of this form of cell death using the mAbs may be potentially therapeutic for subjects with immunological diseases.