Of relevance to our discovery is the finding that eight X-Linked Hyper IgM Syndrome (HIGM1)-causative variants have alterations in the CD40L integrin binding, and they are defective in integrin binding and signaling, suggesting that the loss of integrin binding is related to the defect in CD40L signaling in HIGM1. This evidence concerns the gene CD40LG and X-linked hyper-IgM syndrome.