ESTABLISHMENT OF MAIDS-DEFECTIVE VIRUS-INFECTED B-CELL LINES AND THEIR CHARACTERIZATION

Mice inoculated with the murine AIDS (MAIDS)-defective virus develop s evere B and T cell dysfunctions. The primary event in the development of this disease is the infection and polyclonal expansion of the targe t cells of this defective virus, which have been reported to belong to the B cell lineage. To further study the central role that these cell s play in the development of MAIDS, we attempted to establish MAIDS-de fective virus-infected B cell lines in vitro. We succeeded in establis hing two cell lines, SD1 and CSTB5, from the enlarged organs of C57BL/ 6 mice inoculated with helper-free stocks of the MAIDS-defective virus . Both cell lines are not transplantable in syngeneic C57BL/6 mice or in nude or CD8(-/-) mice and are apparently not malignant. They both b elong to the B lineage, as their immunoglobulin tig) genes, but not th e T cell receptor (TcR) beta locus, are rearranged, suggesting that th ey are relatively mature B cells. However, analysis of cell surface ma rker expression by FAGS revealed a surface phenotype similar to that o f pre-B cells (MHC I+, MHC II+, B7.2(+), slgM(-), slgG(-), kappa(-), B 220(-), CD5(-), Thy1.2(-), TcR-, CD3(-), CD4(-), CD8(-), Mac-1(-), 33D 1(-)). Additionally, the CSTB5 cells express CD40 and the SD1 cells ex press CD43. Both cell lines contain the MA[DS-defective provirus and e xpress the expected 4.2-kb viral RNA and the corresponding pr60(gag) p rotein. The CSTB5 cells are nonproducer, while the SD1 cell line produ ces what appears to be an endogenous MuLV. The phenotype of these cell lines is very similar to what is known about the target B cells of th is virus in vivo. These new established cell lines are likely to be us eful in elucidating the mechanism(s) by which the MAIDS-defective viru s causes its target B cells to proliferate and induce T cell anergy in infected animals. (C) 1998 Academic Press.