Fas ligand-mediated immune surveillance by T cells is essential for the control of spontaneous B cell lymphomas
Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes immunitaires permettant d'expliquer pourquoi des mutations des gènes PRDM1 et BCL6, fréquemment observées chez des patients atteints d'un lymphome diffus à grandes cellules B, n'induisent pas à elles seules le développement de la maladie
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.