The findings described above suggest that two distinct mechanisms are responsible for activation of the BCR pathway in ABC and GCB DLBCL, respectively: an antigen-dependent mechanism resulting in a “chronic active” BCR signal that activates both NF-κB and PI3K and an antigen-independent mechanism resulting in an exaggerated “tonic” BCR signal that activates only PI3K. This evidence concerns the gene NFKB1 and diffuse large B-cell lymphoma.