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 resistance to plasmacytoma induction in mice, however little is known about the cellular aspects of these phenotypes. The complexity of plasmacytomagenesis allows for susceptibility and resistance to reflect differences in B cells, T cells, accessory cells and/or stromal elements contributing to the disease process. Alternatively, these phenotypes may result from differential abilities to affect events critical to plasmacytomagenesis, such as myc deregulation. To address these possibilities, the v-myc-raf-containing retrovirus, J3V1, was used to induce plasmacytomas (PCTs) in severe combined immunodeficient (SCID) mice reconstituted with susceptible (Balb/c) and/or resistant (DBA/2) cells. The results demonstrate that Balb/c bone marrow (BM)-reconstituted SCID mice yielded PCTs of donor origin, while DBA/2 BM-reconstituted mice did not. Mice reconstituted with both DBA/2 BM and Balb/c peripheral lymphocytes, 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 attributable to the inability of DBA/2 B cells to deregulate myc; and (4) potential PCT targets reside in a number of lymphoid tissues. Taken together, these results demonstrate that a major aspect of resistance/susceptibility to plasmacytomagenesis is dictated by the genotype of the target B cell.
Hilbert
D M
DM
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Pumphrey
J G
JG
Troppmair
J
J
Rapp
U R
UR
Rudikoff
S
S
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D018956:CD5 Antigens; D004198:Disease Susceptibility; D005260:Female; D016259:Genes, myc; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D010954:Plasmacytoma / Q000235:genetics / Q000276:immunology*; D012190:Retroviridae / Q000235:genetics*; D013045:Species Specificity; D013729:Terpenes / Q000494:pharmacology
D015703:Antigens, CD; D018956:CD5 Antigens; D013729:Terpenes; C009042:pristane