Fas ligand-mediated immune surveillance by T cells is essential for the control of spontaneous B cell lymphomas

被引：83

作者：

Afshar-Sterle, Shoukat ^{[1
,2
]}

Zotos, Dimitra ^{[1
,2
]}

Bernard, Nicholas J. ^{[1
,2
]}

Scherger, Anna K. ^{[1
,2
]}

Roedling, Lisa ^{[1
,2
]}

Alsop, Amber E. ^{[1
,2
]}

Walker, Jennifer ^{[1
,2
]}

Masson, Frederick ^{[1
,2
]}

Belz, Gabrielle T. ^{[1
,2
]}

Corcoran, Lynn M. ^{[1
,2
]}

O'Reilly, Lorraine A. ^{[1
,2
]}

Strasser, Andreas ^{[1
,2
]}

Smyth, Mark J. ^{[3
,4
]}

Johnstone, Ricky ^{[5
,6
]}

Tarlinton, David M. ^{[1
,2
]}

Nutt, Stephen L. ^{[1
,2
]}

Kallies, Axel ^{[1
,2
]}

机构：

[1] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia

[3] QIMR Berghofer Med Res Inst, Immunol Canc & Infect Lab, Herston, Qld, Australia

[4] Univ Queensland, Sch Med, Herston, Qld, Australia

[5] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia

[6] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia

来源：

NATURE MEDICINE | 2014年 / 20卷 / 03期

基金：

英国医学研究理事会;

关键词：

NF-KAPPA-B; CLASS SWITCH RECOMBINATION; CYTIDINE DEAMINASE AID; SOMATIC HYPERMUTATION; PROTEIN EXPRESSION; GENE; PATHOGENESIS; MUTATIONS; RECEPTOR; CANCER;

D O I：

10.1038/nm.3442

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：283 / 290

页数：8

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