The Direction of Plasma Membrane Exchange between Lymphocytes and Accessory Cells by Trogocytosis Is Influenced by the Nature of the Accessory Cell
The Direction of Plasma Membrane Exchange between Lymphocytes and Accessory Cells by Trogocytosis Is Influenced by the Nature of the Accessory Cell
复制标题
DOI：
10.4049/jimmunol.0901570
复制
发表时间：
2010-02-15
影响因子：
4.4
通讯作者：
Hudrisier, Denis
中科院分区：
文献类型：
--
作者：
Daubeuf, Sandrine;Lindorfer, Margaret A.;Hudrisier, Denis
在淋巴细胞与其细胞伴侣之间形成的结合物中，质膜片段（包括细胞表面蛋白和脂质）的交换是一个深入研究的领域。除了其在Ag识别过程中的自然发生之外，当Ab靶向的淋巴细胞与表达Fe γ R的辅助细胞缀合时，可以在实验或治疗环境中触发膜转移过程。膜捕获的方向（即，两个细胞中的哪一个将捐献或接受质膜片段）可以具有重要的功能性后果，例如肿瘤细胞对治疗性mAb的治疗不敏感。这种效应称为抗原调节或剃除，是Fc γ R表达细胞从肿瘤细胞中去除mAb及其靶蛋白的过程的结果。因此，我们分析了在各种Fc γ R表达细胞与一系列正常或肿瘤T和B细胞之间形成的缀合物中的该过程，所述T和B细胞用能够触发膜交换的不同Ab（包括治疗性Ab利妥昔单抗）调理。我们的研究结果表明，膜捕获的方向是由Fc γ R表达细胞的身份决定的，比淋巴细胞或所用抗体的类型更重要。我们发现单核细胞和巨噬细胞倾向于参与与调理靶细胞的双向胞吞作用，这是一个与吞噬作用平行的过程。我们的观察打开了新的视角，以了解参与胞啃的机制，并可能有助于优化抗体为基础的免疫方法。免疫学杂志，2010，184：1897-1908。
Exchange of plasma membrane fragments, including cell-surface proteins and lipids, in conjugates formed between lymphocytes and their cellular partners is a field of intense investigation. Apart from its natural occurrence during Ag recognition, the process of membrane transfer can be triggered in experimental or therapeutic settings when lymphocytes targeted by Abs are conjugated to Fe gamma R-expressing accessory cells. The direction of membrane capture (i.e., which of the two cells is going to donate or accept plasma membrane fragments) can have important functional consequences, such as insensitivity of tumor cells to treatment by therapeutic mAbs. This effect, called antigenic modulation or shaving, occurs as a result of a process in which the Fc gamma R-expressing cells remove the mAb and its target protein from the tumor cells. We therefore analyzed this process in conjugates formed between various Fc gamma R-expressing cells and a series of normal or tumor T and B cells opsonized with different Abs capable of triggering membrane exchange (including the therapeutic Ab rituximab). Our results show that the direction of membrane capture is dictated by the identity of the Fc gamma R-expressing cell, much more so than the type of lymphocyte or the Ab used. We found that monocytes and macrophages are prone to be involved in bidirectional trogocytosis with opsonized target cells, a process they can perform in parallel to phagocytosis. Our observations open new perspectives to understand the mechanisms involved in trogocytosis and may contribute to optimization of Ab-based immunotherapeutic approaches. The Journal of Immunology, 2010,184: 1897-1908.