CD40 and hyper-IgM syndrome: A fundamental role for NF-κB signaling in the GC reaction was always expected: the stimulation of CD40 on B cells by CD154 expressed on T helper cells activates NF-κB, and inherited germline mutations in the CD40 and CD154 genes that impair CD40-CD154 co-stimulation cause the Hyper-IgM syndrome, in which GCs are absent [43].