In the setting of life-threatening fungal infections such as those caused by Candida spp., Aspergillus spp., and Cryptococcus spp., the structural properties of IgM, particularly its pentameric configuration and multivalent binding capacity, enable potent interactions with the highly repetitive carbohydrate and mannoprotein epitopes abundant on fungal cell walls. This evidence concerns the gene CD40LG and fungal infectious disease.