We choose this signature of p65 activation because it hallmarks synergy between TLR9 signaling, cytokine milieu and BCR signaling in promoting clonal expansion of chronic lymphocytic leukemia cells (27, 28), and because the BCR-mediated phosphorylation of p65(pS529) is defective in CD21low B cells of CVID patients (29). The gene discussed is TLR9; the disease is B-cell chronic lymphocytic leukemia.