Germinal Centers: Gaining Strength from the Dark Side Jason G. Cyster  Immunity  Volume 43, Issue 6, Pages 1026-1028 (December 2015) DOI: 10.1016/j.immuni.2015.11.019 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 Essential Role of Foxo1 in the GC DZ B Cell Program In the LZ state, pAkt is abundant probably due to high PI3K activity, and Foxo1 levels are low. In the DZ state, pAkt is low at least in part due to PTEN activity, and Foxo1 accumulates in the nucleus to positively regulate the expression of many DZ-state-associated genes including CXCR4 while contributing to represssion of Blimp1 and a range of LZ-state-associated genes, in some cases cooperating with Bcl6. The nature of the signals promoting PI3K and pAkt activity in the LZ are not fully defined but are likely to include the BCR. It is possible that signals in addition to pAkt are involved in repressing Foxo1. The signals favoring Foxo1 activation are also unclear but inputs from Tfh cells might be a trigger. Tfh-cell-derived signals, including CD40L, promote NF-κB activity and c-myc induction. Dashed arrows indicate connections that are not fully established. PTEN, phosphatase and tensin homolog. Immunity 2015 43, 1026-1028DOI: (10.1016/j.immuni.2015.11.019) Copyright © 2015 Elsevier Inc. Terms and Conditions