Skip to main content
. Author manuscript; available in PMC: 2009 Sep 22.
Published in final edited form as: Curr Opin Hematol. 2008 Jul;15(4):381–390. doi: 10.1097/MOH.0b013e328302c7df

Figure 2. Inhibitory mechanisms for BCL6 function or expression.

Figure 2

A: Reversible inhibition of BCL6 through transient CD40 signaling: CD40 signaling triggers NFkB activity, which results in dissociation of the BCL6-N-CoR complex and release of BCL6 repression of checkpoint genes. This allows cells to undergo a DNA damage sensing quality control step leading to apoptosis if damage is severe; or once CD40 signaling ceases, to undergo additional rounds of affinity maturation, or to proceed to terminal differentiation. B: ATM induced BCL6 protein degradation. High levels of DNA damage trigger an ATM dependent cascade that results in BCL6 phosphorylation and association with PIN1, followed by proteolytic degradation of BCL6 and apoptosis. C: CD40 mediated transcriptional downregulation of BCL6. Sustained contact between FDCs and B-cells leads to NFkB induction of IRF4, which can repress BCL6, while at the same time cytokines can trigger JAK-STAT pathways whereby STAT5 can also repress BCL6. This leads to terminal differentiation of selected high affinity immunoglobulin producing cells.