Fig. 2: NF-Kb and CREBBP effects on terminal B-cell differentiation and GC exit. | Modern Pathology

Fig. 2: NF-Kb and CREBBP effects on terminal B-cell differentiation and GC exit.

From: Evolving insights into the genomic complexity and immune landscape of diffuse large B-cell lymphoma: opportunities for novel biomarkers

Fig. 2

Activation of NF-kB leads to upregulation of IRF4, which is critical for terminal B-cell differentiation. IRF4 can repress BCL-6 through the induction of BLIMP1, which is required to initiate the plasma cell program. In a physiologic state, BCL-6 function is impaired by CREBBP-mediated acetylation. CREBBP mutations result in either loss of function or dominant negative effects, that in turn lead to failure to induce acetylation of BCL-6 target enhancers, preventing the termination of BCL6 transcriptional program. GC germinal center.

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