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Animal Models

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 μ locus and c-myc

Abstract

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-2LD 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 Cμ locus (5′-Cμ) and c-myc(5′-Cμ/c-myc+ clones). Similar 5′-Cμ/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′-Cμ and c-myc. Taken in conjunction with our previous observation that 5′-Cμ/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.

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Acknowledgements

We are grateful to Dr Michael Potter for providing BALB/c.IL-6 mice and numerous insightful discussions throughout the experiments. We acknowledge the staff of our mouse colony, particularly Wendy DuBois, for animal husbandry. We thank Dr Rebecca Liddell for reading the manuscript and making helpful editorial suggestions. We also thank EB Mushinski for performing immunostaining.

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Kovalchuk, A., Kishimoto, T. & Janz, S. 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 μ locus and c-myc. Leukemia 14, 1127–1135 (2000). https://doi.org/10.1038/sj.leu.2401767

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