Statement of significance: Loss ofTFL, found in several types of lymphoma, induces excessive CXCL13 secretion through RNA dysregulation contributing to body weight loss and early death in lymphoma model mice. Follicular lymphoma (FL) is associated with overexpressed BCL-2 and other genetic aberrations, including 6q-. We identified a novel gene on 6q25, “Transformed follicular lymphoma(TFL),” from a transformed FL. TFL regulates several cytokinesviamRNA degradation, which has been suggested to underlie resolving inflammation. Fluorescencein situhybridization revealed a deletion ofTFLoccurred in 13.6% of various B-cell lymphoma samples. We developed VavP-bcl2transgenic, TFL deficit mice (Bcl2-Tg/Tfl-/-) to seek how TFL affects disease progression in this lymphoma model. WhileBcl2-Tg mice developed lymphadenopathy and died around 50 weeks,Bcl2-Tg/Tfl-/-mice lost body weight around 30 weeks and died about 20 weeks earlier thanBcl2-Tg mice. Furthermore, we found a unique B220-IgM+cell population in the bone marrow ofBcl2-Tg mice. cDNA array in this population revealed that Cxcl13 mRNA inBcl2-Tg/Tfl-/-mice expressed significantly higher thanBcl2-Tg mice. In addition, bone marrow extracellular fluid and serum showed an extremely high Cxcl13 concentration inBcl2-Tg/Tfl-/-mice. Among bone marrow cells, the B220-IgM+fraction was the main producer of Cxcl13 in culture. A reporter assay demonstrated TFL regulates CXCL-13viainduction of 3’UTR mRNA degradation in B lineage cells. These data suggest Tfl regulates Cxcl13 in B220-IgM+cells in the bone marrow, and a very high concentration of serum Cxcl13 arising from these cells may contribute to early death in lymphoma-bearing mice. Since several reports have suggested the association of CXCL13 expression with lymphoma, these findings provide new insights into cytokine regulationviaTFL in lymphoma.