SUSCEPTIBILITY AND RESISTANCE TO J3V1 RETROVIRUS-INDUCED MURINE PLASMACYTOMAGENESIS IN RECONSTITUTED SEVERE COMBINED IMMUNODEFICIENT MICE

To date much is known about the genetics of susceptibility and resista nce to plasmacytoma induction in mice, however little is known about t he cellular aspects of these phenotypes. The complexity of plasmacytom agenesis allows for susceptibility and resistance to reflect differenc es in B cells, T cells, accessory cells and/or stromal elements contri buting to the disease process. Alternatively, these phenotypes may res ult from differential abilities to affect events critical to plasmacyt omagenesis, such as myc deregulation. To address these possibilities, the v-myc-raf-containing retrovirus, J3V1, was used to induce plasmacy tomas (PCTs) in severe combined immunodeficient (SCID) mice reconstitu ted with susceptible (Balb/c) and/or resistant (DBA/2) cells. The resu lts demonstrate that Balb/c bone marrow (BM)-reconstituted SCID mice y ielded PCTs of donor origin, while DBA/2 BM-reconstituted mice did not . Mice reconstituted with both DBA/2 BM and Balb/c peripheral lymphocy tes, as well as those reconstituted with Balb/c peripheral lymphocytes alone, also yielded only Balb/c PCTs. These results indicate that: (1 ) a microenvironment supportive of plasmacytomagenesis is insufficient to allow PCT development among resistant cells; (2) DBA/ 2 BM-derived cells do not suppress plasmacytomagenesis by target cell elimination or microenvironment destruction; (3) resistance is not solely attribut able to the inability of DBA/2 B cells to deregulate myc; and (4) pote ntial PCT targets reside in a number of lymphoid tissues. Taken togeth er, these results demonstrate that a major aspect of resistance/suscep tibility to plasmacytomagenesis is dictated by the genotype of the tar get B cell.