In summary, our study suggests that impaired demethylation in the transition from naïve to memory B cells in CpGs at genes implicated in B cell signaling and survival (STAT3, AKT1, FOXO, and NFKB2), and at genes required for the GC reaction (AICDA and BCL6) might contribute to the terminal B cell defect in CVID patients. Here, AKT1 is linked to common variable immunodeficiency.