A Novel Type of Cell Death of Lymphocytes induced by mAb

我们早前发现，一种大鼠单克隆抗体（mAb） RE2能以补体不依赖的方式诱导激活而非静止的小鼠淋巴细胞快速死亡，这种细胞死亡不同于典型的细胞凋亡或坏死。我们发现这种细胞死亡不依赖于Fas和半胱天冬酶。我们发现RE2表位位于小鼠ia2类结构域。然而，a3结构域在转导死亡信号中起关键作用，介导MHC I类-整合肌动蛋白丝系统的广泛聚集，产生膜孔。在T细胞活化相关的暴发性肝炎小鼠模型中，mAb RE2几乎完全抑制肝细胞损伤的发展。使用单克隆抗体诱导这种形式的细胞死亡可能对免疫疾病患者有潜在的治疗作用。

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.