META-controlled env-initiated transcripts encoding superantigens of murineMtv29 and Mtv7 and their possible role in B cell lymphomagenesis

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. Th e encoded vSAg29 stimulates syngeneic V beta 16(+) CD4(+) T cells, thereby acquiring T cell help necessary for RCS growth. Other strains of B cell lym phoma-prone mice include mtv29(+) C57L and MA/MyJ, and the Mtv29(-) Mtv7(+) -recombinant inbred strain, SW X J-1. The lymphomas of these mice produce s imilar mouse mtv-vSAg-encoding mRNA, as characterized by Northern blotting, PCR, and RNase protection. A 1.8-kb mRNA in C57L/J and MA/MyJ lymphomas hy bridized with an Mtv29-specific oligonucleotide, whereas SW X J-1 lymphomas produced 1.8-kb transcripts hybridizing with an Mtv7-specific oligonucleot ide. Similar META-env-initiated transcripts were absent from LPS-activated B cells from any strain examined but were detected in Peyer's patch RNA fro m SJL mice. Like typical SJL-derived RCS, all these lymphomas stimulated sy ngeneic CD4(+) T cells and V beta 16(+) T hybridoma cells. Immunohistochemi cal staining of primary tumors showed the presence of peanut agglutinin bin ding (PNA(+)) highly mitotic lymphoblasts, suggesting their GC derivation. The findings indicate that this novel mRNA for Mtv29 is present in B cell l ymphomas from several Mtv29(+) mouse strains. Additionally, this is the fir st description of the ability of Mtv7 to produce transcripts that are contr olled and spliced identically to those of Mtv29 and that are expressed in S W X J-1, I-A(s+), lymphomas that also stimulate V beta 16(+) T cells. Our r esults suggest an important role for mouse mtv-vSAgs and V beta 16(+) T cel l stimulation in the development of GC-derived murine B cell lymphomas.