Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France.
J Immunol. 2010 Feb 15;184(4):1897-908. doi: 10.4049/jimmunol.0901570. Epub 2010 Jan 20.
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 FcgammaR-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 FcgammaR-expressing cells remove the mAb and its target protein from the tumor cells. We therefore analyzed this process in conjugates formed between various FcgammaR-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 FcgammaR-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.
淋巴细胞与其细胞伙伴形成的合体之间的质膜片段(包括细胞表面蛋白和脂质)交换是一个研究热点。除了在 Ag 识别过程中的自然发生外,当被 Abs 靶向的淋巴细胞与表达 FcγR 的辅助细胞共轭时,质膜转移过程可以在实验或治疗环境中被触发。质膜捕获的方向(即两个细胞中的哪一个将捐赠或接受质膜片段)可能具有重要的功能后果,例如肿瘤细胞对治疗性 mAb 治疗的不敏感性。这种效应称为抗原性调节或削除,是由于表达 FcγR 的细胞从肿瘤细胞中去除 mAb 和其靶蛋白的过程。因此,我们分析了各种表达 FcγR 的细胞与一系列正常或肿瘤 T 和 B 细胞之间形成的合体中的这一过程,这些细胞被不同的能够触发质膜交换的 Abs(包括治疗性 Ab 利妥昔单抗)包被。我们的结果表明,质膜捕获的方向取决于表达 FcγR 的细胞的身份,而不是淋巴细胞的类型或使用的 Abs。我们发现单核细胞和巨噬细胞容易与被包被的靶细胞发生双向 trogocytosis,它们可以与吞噬作用并行进行这一过程。我们的观察结果为理解 trogocytosis 涉及的机制开辟了新的视角,并可能有助于优化基于 Ab 的免疫治疗方法。