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

Immune surveillance has been proposed to eliminate transformed cells and thereby limit tumor formation. Axel Kallies and colleagues now report that spontaneous B cell lymphoma development in Blimp1-deficient or Bcl6-overexpressing mice is accelerated by T cell deficiency and identify the Fas-Fas ligand pathway as a crucial mediator of T cell control of lymphoma growth. 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.