Follicular lymphoma is a common B cell-derived malignancy that often follows a prolonged indolent phase followed by a terminal aggressive phase. The growth requirements for follicular lymphomas are poorly understood. B cells from patients with follicular lymphoma die rapidly when grown in culture. We have been able to keep B cells from patients with follicular lymphomas alive in vitro for 20 days using native Interleukin 14 (IL-14) which was originally identified as a B cell growth factor. Native IL-14 contains two molecules produced from the IL14 gene, IL-14α and IL-14β. Interleukin 14α utilizes exons 3-10 while IL-14β is produced from the opposite strand of the IL14 gene to IL-14α and utilizes only exon 10. We have previously demonstrated that transgenic mice expressing IL-14α develop autoimmunity and large B cell lymphomas. In this manuscript we demonstrate that IL-14β transgenic mice develop lymphomas that closely resemble follicular lymphoma. When IL-14β Tg mice are crossed with c-Myc transgenic mice, the Double Transgenic mice (DTgβ) are born with lymphomas resembling the aggressive phase of follicular lymphoma. We also demonstrate that the mRNA for IL-14β is expressed constitutively in normal B cells, T cells and follicular dendritic cells as well as in the Burkitt lymphoma line Namalva. The expression of IL-14β mRNA is decreased with cell activation and in the spleen cells of autoimmune (NZBxNZW) F1 mice. Thus, IL-14β is a distinct protein with differential regulation and physiological effects from IL-14α. IL-14β Tg mice and DTgβ mice are new animal models to study the dormant and aggressive phases of follicular lymphoma.
Jingxiu Xuan, Long Shen, Chongjie Zhang, Richard J. Ford and Julian L. Ambrus, 2012. IL-14β Transgenic Mice Develop Tumors Consistent with Follicular Lymphoma. International Journal of Cancer Research, 8: 83-94.