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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / cytology
  • Cell Separation
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Fas Ligand Protein / metabolism*
  • Flow Cytometry
  • Genes, Tumor Suppressor
  • Immunologic Surveillance / genetics
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Mice
  • Mice, Transgenic
  • Mutation
  • Positive Regulatory Domain I-Binding Factor 1
  • Proto-Oncogene Proteins c-bcl-6
  • T-Lymphocytes / immunology*
  • Transcription Factors / genetics*
  • Transcription Factors / physiology


  • Bcl6 protein, mouse
  • DNA-Binding Proteins
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Prdm1 protein, mouse
  • Proto-Oncogene Proteins c-bcl-6
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1