T 细胞介导的 Fas 配体免疫监视对于控制自发性 B 细胞淋巴瘤是至关重要的。
Fas ligand-mediated immune surveillance by T cells is essential for the control of spontaneous B cell lymphomas.
机构信息
1] Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia. [3].
1] Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
出版信息
Nat Med. 2014 Mar;20(3):283-90. doi: 10.1038/nm.3442. Epub 2014 Feb 2.
Loss of function of the tumor suppressor gene PRDM1 (also known as BLIMP1) or deregulated expression of the oncogene BCL6 occurs in a large proportion of diffuse large B cell lymphoma (DLBCL) cases. However, targeted mutation of either gene in mice leads to only slow and infrequent development of malignant lymphoma, and despite frequent mutation of BCL6 in activated B cells of healthy individuals, lymphoma development is rare. Here we show that T cells prevent the development of overt lymphoma in mice caused by Blimp1 deficiency or overexpression of Bcl6 in the B cell lineage. Impairment of T cell control results in rapid development of DLBCL-like disease, which can be eradicated by polyclonal CD8(+) T cells in a T cell receptor-, CD28- and Fas ligand-dependent manner. Thus, malignant transformation of mature B cells requires mutations that impair intrinsic differentiation processes and permit escape from T cell-mediated tumor surveillance.
抑癌基因 PRDM1（也称为 BLIMP1）的功能丧失或致癌基因 BCL6 的表达失调，发生在很大一部分弥漫性大 B 细胞淋巴瘤（DLBCL）病例中。然而，在小鼠中靶向突变这两个基因只会导致恶性淋巴瘤的缓慢和偶尔发生，尽管健康个体的活化 B 细胞中经常发生 BCL6 突变，但淋巴瘤的发展却很少见。在这里，我们表明 T 细胞可防止由 Blimp1 缺陷或 Bcl6 在 B 细胞谱系中的过表达引起的小鼠明显淋巴瘤的发展。T 细胞控制的损害会导致类似于 DLBCL 的疾病迅速发展，这种疾病可以通过多克隆 CD8(+)T 细胞以 TCR、CD28 和 Fas 配体依赖的方式消除。因此，成熟 B 细胞的恶性转化需要突变，这些突变会损害内在的分化过程，并允许逃避 T 细胞介导的肿瘤监视。
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