IL-14β transgenic mice develop tumors consistent with follicular lymphoma

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 ILI4 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 (NZB×NZW) FI 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.