CD40 encoded by TNFRSF5 gene is a key receptor regulating immunoglobulin class switch recombination (CSR) and differentiation into memory B cells and plasma cells; individuals with loss-of-function mutations in the TNFRSF5 gene develop hyper-IgM syndrome type 3 (HIGM3), a severe primary immunodeficiency characterized by normal or elevated serum IgM levels and decreased levels or absence of both IgG and IgA, resulting in susceptibility to bacterial infections [33]. The gene discussed is CD40LG; the disease is hyper-IgM syndrome type 3.