META-Controlled ev-initiated transcripts encoding superantigens of murine Mtv29 and Mtv7 and Their Possible Role in B Cell Lymphomagenesis

摘要

Spontaneous germinal center (GC)-derived B cell lymphomas of SJL mice (RCS) transcribe a 1.8-kb Mtv-29 mRNA under control of the META-env promoter. The encoded vSAg29 stimulates syngeneic VI316~ CD4~ T cells, thereby acquiring T cell help necessary for RCS growth. Other strains of B cell lymphoma-prone mice include Mtv29~ C57L and MAI1VIyJ, and the Mtv29 Mtv7~-recombinant inbred strain, SW x J-1. The lymphomas of these mice produce similar mouse mtv-vSAg-encoding mRNA, as characterized by Northern blotting, PCR, and RNase protection. A 1.8-kb mRNA in CS7L/J and MAIIVIyJ lymphomas hybridized with an Mtv29-specific oligonucleotide, whereas SW x J-1 lymphomas produced 1.8-kb transcripts hybridizing with an Mtv7-specific oligonucleotide. Similar META-env-initiated transcripts were absent from LPS-activated B cells from any strain examined but were detected in Peyer’s patch RNA from 5Th mice. Like typical SJL-derived RCS, all these lymphomas stimulated syngeneic CD4~ T cells and VI316~ I hybridoma cells. Immunohistochemical staining of primary tumors showed the presence of peanut agglutinin binding (PNA~) highly mitotic lymphoblasts, suggesting their GC derivation. The findings indicate that this novel mRNA for Mtv29 is present in B cell lymphomas from several Mtv29 + mouse strains. Additionally, this is the first description of the ability of Mtv7 to produce transcripts that are controlled and spliced identically to those of Mtv29 and that are expressed in SW X J-1, L~As+, lymphomas that also stimulate Vf316~ T cells. Our results suggest an important role for mouse mtv-vSAgs and V1316 T cell stimulation in the development of GC-derived murine B cell lymphomas.