Influenza Virus-Specific Neutralizing IgM Antibodies Persist for a Lifetime

Detection of immunoglobulinM (IgM) antibodies has long been used as an important diagnostic tool for identifying active viral infections, but their relevance in later stages has not been clearly defined in vivo. In this study, we followed the kinetics, longev-ity, and function of influenza virus-specific IgM antibodies for 2 years following sublethal infection of mice with live mouse-adapted A/PR/8/34 virus or immunization with formalin-inactivated virus. These groups mounted robust protective immune responses and survived lethal challenges with 50 50 % lethal dose (LD50) mouse-adapted A/PR/8/34 virus 600 days after the primary exposure. Surprisingly, the virus-specific IgM antibodies persisted along with IgG antibodies, and we found a signifi-cantly higher number of IgM-positive (IgM) virus-specific plasma cells than IgG plasma cells that persisted for at least 9 months postexposure. The IgM antibodies were functional as they neutralized influenza virus in the presence of complement just as well as IgG antibodies did. Influenza is a common infectious disease of the respiratory sys-tem caused by a negative-sense, single-stranded RNA virus, which belongs in theOrthomyxoviridae family. The most virulent strains belong to type A influenza, and their classification is based on the antigenic differences of their major surface antigens, hem-agglutinin (HA) and neuraminidase (NA), which arose from the gene segment exchange between the avian and human pools