Together with our results, the inactivation of BTK kinase activity in DLBCL cells, although not impacting BCR signaling, may weaken the crosstalk between BCR and TLR9 signaling, resulting in increased dependency on TLR9. The biochemical and functional interactions between TLR9 and kinase-inactive BTK warrant future studies. Here, BTK is linked to diffuse large B-cell lymphoma.