Humans as well as mice lacking CD40–CD40L interactions fail to develop GC and characteristically present with hyper-IgM syndrome, i.e., high levels of IgM but little switched antibodies in serum, no TD antigen responses and lack of switched memory B cells (Kawabe et al., 1994; Xu et al., 1994; Weller et al., 2001). This evidence concerns the gene CD40LG and thanatophoric dysplasia.