Additionally, these IgM-NAA, by virtue of being polyreactive, also cross-react with pathogen-expressed molecules, for example, PC on Streptococcus pneumoniae and other antigens expressed by various viruses and parasites (55–57) Hence, it has been suggested that these natural IgM antibodies are protective, serving as a first line of defense against infections and protecting the host from pathogen-mediated apoptotic cells and oxidized neo-determinants that can induce pathogenic IgG autoantibodies (55, 56). Here, CD40LG is linked to infection.