Lymph nodes and Peyer's patches of IL-6 transgenic BALB/c mice harbor T(12;15) translocated plasma cells that contain illegitimate exchanges between the immunoglobulin heavy-chain mu locus and c-myc.
Hyperplastic plasmacytotic lymph nodes and Peyer's patches of 12 of 25 (48%) BALB/c mice that carried a human IL-6 transgene under the transcriptional control of the histocompatibility H-2L(D) promoter (BALB/c.IL-6 mice) were found to harbor 15 cell clones that contained in their T(12;15) translocation breakpoint regions illegitimate genetic recombinations between the upstream flank of the immunoglobulin heavy-chain C mu locus (5'-C mu) and c-myc (5'-C mu/c-myc+ clones). Similar 5'-C mu/c-myc+ clones were also detected in pristane-induced peritoneal granulomata (a significant source of IL-6 in situ) of three of 13 (13%) conventional BALB/c mice, but not in lymphoid tissues of pristane-treated BALB/c mice, nor in any tissue of untreated BALB/c mice. These findings provided strong evidence that IL-6 may be able to promote the growth and/or survival of clones that contained rearrangements between 5'-C mu and c-myc. Taken in conjunction with our previous observation that 5'-C mu/c-myc+ clones are the precursors for pristane-induced BALB/c plasmacytomas, the findings further suggested that IL-6 may play a pivotal role in the early stage of plasmacytoma development, by promoting tumor precursor cells. The BALB/c.IL-6 model of plasmacytomagenesis may be superior to the conventional BALA/c model because the putative plasmacytoma precursors appear to be more prevalent and in their development independent of treating the mice with inflammation-inducing plasmacytomagenic agents, such as pristane or silicone polymers.
Kovalchuk
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AL
Laboratory of Genetics, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Kishimoto
T
T
Janz
S
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D000818:Animals; D001483:Base Sequence; D002881:Chromosomes, Human, Pair 12; D002884:Chromosomes, Human, Pair 15; D017931:DNA Primers; D016259:Genes, myc; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000276:immunology / Q000473:pathology*; D010950:Plasma Cells / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic
D017931:DNA Primers; D007148:Immunoglobulin mu-Chains; D015850:Interleukin-6