Newly discovered and conserved role of IgM against viral infection in an early vertebrate.

IgM emerged in jawed vertebrates 500 Mya and remains the most evolutionarily conserved antibody class. However, despite extensive studies on IgM as an ancient antiviral weapon in warm-blooded vertebrates, its role and mechanisms in combating viral infections in early vertebrates remain poorly understood. Here, significant virus-specific sIgM titers are generated in the serum and gut mucus of a teleost fish (largemouth bass) that survive infection, and fish lacking sIgM were more susceptible to viral infection. These results challenge the paradigm that IgM and IgT are specialized to systemic and mucosal immunity, respectively. More crucially, the neutralization assay provides further insight into the role of sIgM in viral neutralization and clarifies the mechanism through which teleost sIgM blocks viral infection by directly targeting viral particles. From an evolutionary perspective, sIgM in both primitive and modern vertebrates follows conserved principles in the development of specialized antiviral immunity.