Immunologic induction of malignant lymphoma: graft-vs-host reaction-induced B cell lymphomas contain integrations of predominantly ecotropic murine leukemia proviruses

The induction of a graft-vs-host reaction in (BALB/c X A)F1 mice by i.v. injection with BALB/c lymphoid cells leads to a lymphoid hyperplasia that may progress to malignant lymphoma. In the present paper, the following aspects of graft-vs-host-reaction lymphomagenesis were studied: 1) the cellular requirements for the induction of lymphomas, 2) their cellular origin, and 3) the role of murine leukemia viruses. The development of graft-vs-host-reaction lymphomas was found to be mediated by donor T cells and to require the presence of histoincompatibility between donor and host. Histologically, the vast majority of these lymphomas were either of follicular center cell or of immunoblastic type, whereas immunoperoxidase studies showed that they were virtually all B cell derived. Most of the lymphomas were of host origin. In the DNA of approximately 80% of the lymphomas, integrated murine leukemia virus proviruses were detected. In the B cell lymphoma DNA, integrated ecotropic proviruses prevailed, but recombinant murine leukemia virus and/or deleted murine leukemia virus genomes were also detected in some tumor DNA.