학술논문
Fas ligand-mediated immune surveillance by T cells is essential for the control of spontaneous B cell lymphomas.
Document Type
Article
Author
Afshar-Sterle, Shoukat; Zotos, Dimitra; Bernard, Nicholas J; Scherger, Anna K; Rödling, Lisa; Alsop, Amber E; Walker, Jennifer; Masson, Frederick; Belz, Gabrielle T; Corcoran, Lynn M; O'Reilly, Lorraine A; Strasser, Andreas; Smyth, Mark J; Johnstone, Ricky; Tarlinton, David M; Nutt, Stephen L; Kallies, Axel
Source
Subject
*FAS proteins
*IMMUNE system
*T cells
*B cell lymphoma
*TUMOR suppressor genes
*LABORATORY mice
*
*
*
*
*
Language
ISSN
1078-8956
Abstract
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. [ABSTRACT FROM AUTHOR]