Altered PI3K signaling may well also contribute to the immunodeficiency in CVID as PI3K signal strength, and the dynamic regulation of transcription factors, such as FOXO1 and HIF1α, determines the selection into short-lived plasmablasts or germinal center B-cell fate, the induction of somatic hyper mutation and class switch recombination and finally the integrity of memory and plasma cell formation [54,55,62,70,71]. Here, FOXO1 is linked to immunodeficiency disease.