Defects in CD40 are the cause of hyper-IgM immunodeficiency syndrome type 3 (HIGM3); also known as hyper-IgM syndrome 3. HIGM3 is an autosomal recessive disorder which includes an inability of B cells to undergo isotype switching, one of the final differentiation steps in the humoral immune system, an inability to mount an antibody-specific immune response, and a lack of germinal center formation.