Figure 8.

DNA damage response regulation in the germinal center. In the germinal center, centroblast undergo rapid proliferation, and expression of activation-induced cytidine deaminase (AID) is initiated. Moreover, centroblasts in the dark zone (DZ) and centrocytes in the light zone (LZ) are prone to undergo apoptosis as they express apoptosis-inducing genes (indicated in the black frame), such as FAS and BAX, and lack expression of the anti-apoptotic gene BCL2. During affinity maturation in the germinal center reaction, B cells that acquire sufficient T-cell help, based on the affinity of their B-cell receptors, are positively selected and rescued from apoptosis. At the same time, DNA damage caused by replication errors and AID-induced lesions (indicated in the black box) trigger a DNA damage response that may activate a p53-dependent apoptosis response, which is counteracted by the B-cell lymphoma 6 (BCL6) protein. Arrows represent positive regulation (activation); T-bars represent negative regulation (inhibition).