Scheme depicting the regulation and biological effects of IκBζ in ABC DLBCL. Somatic oncogenic mutations (asterisks) in the BCR signaling pathway (CD79A, CD79B, and CARD11) or in MYD88 lead to constitutive canonical IKK/NF-κB activation and promote IκBζ expression in ABC DLBCL cells. IκBζ contributes to expression of the NF-κB gene signature that includes survival factors (eg, BCL-XL) as well as the cytokines IL-6 and IL-10. JAK1-STAT3 is activated by autocrine action of IL-6 and IL-10. As STAT3 is able to induce IκBζ expression, the data indicate the potential existence of an autoregulatory feed-forward loop to enhance IκBζ expression and survival function. Mechanistically, IκBζ bind to p50 and p52 and can directly confer transactivation potential to these transcriptionally inactive homodimers. Alternatively, IκBζ may displace p50 (or also p52) homodimers to allow promoter occupancy of active NF-κB p50/p65 heterodimers. BCR, B-cell receptor.