Immunoglobulin M: An Ancient Antiviral Weapon - Rediscovered

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Immunoglobulin M (IgM) is an ancient antibody class found in all vertebrates.
• Previously, IgM was considered a perfect pentamer, but recent research reveals its asymmetric structure.

Purpose of the Study:

• To elucidate the novel structure and functions of IgM.
• To explore IgM's potential in preventing viral infections and informing vaccine development.

Main Methods:

• Structural analysis of IgM revealed an asymmetric, quasi-hexameric form with a gap.
• Investigated IgM's role in carrying the apoptosis inhibitor of macrophages (AIM).
• Assessed the efficacy of mucosal passive immunization with recombinant IgM against simian-human immunodeficiency virus (SHIV) in non-human primates.
• Identified long-lived IgM plasma cells in the spleen producing somatically hypermutated IgM.

Main Results:

• IgM's asymmetric structure facilitates the transport of AIM, aiding in the clearance of cellular debris, cancer cells, and pathogens.
• Mucosal passive immunization with IgM demonstrated proof-of-concept for preventing SHIV transmission in non-human primates.
• Long-lived IgM plasma cells in the spleen produce mutated IgM, providing protection against lethal influenza challenge in mice, even a year after immunization.

Conclusions:

• IgM's structure and function extend beyond its initial role as a first responder.
• IgM-based strategies, particularly involving long-lived plasma cells, show promise for developing novel vaccines against viral acquisition.