B-1 and B-2 Cell–Derived Immunoglobulin M Antibodies Are Nonredundant Components of the Protective Response to Influenza Virus Infection
By N. Baumgarth, O. Herman, G. C. Jager, L. Brown, Leonore Herzenberg, Jianzhu Chen. Journal of Experimental Medicine, 2000
612 citations recorded by the source corpus.
We have studied the role of secreted immunoglobulin (Ig)M in protection from infection with influenza virus and delineated the relative contributions of B-1 versus B-2 cell–derived IgM in this process. Mice deficient in secreted IgM but capable of expressing surface IgM and secreting other Ig classes show significantly reduced virus clearance and survival rates compared with wild-type controls. Irradiation chimeras in which only either B-1 or B-2 cells lack the ability to secrete IgM show mortality rates similar to those of mice in which neither B-1 nor B-2 cells secrete IgM. Dependence on both sources of IgM for survival is partially explained by findings in allotype chimeras that broadly cross-reactive B-1 cell–derived natural IgM is present before infection, whereas virus strain–specific, B-2 cell–derived IgM appears only after infection. Furthermore, lack of IgM secreted from one or both sources significantly impairs the antiviral IgG response. Reconstitution of chimeras lacking B-1 cell–derived IgM only with IgM-containing serum from noninfected mice improved both survival rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be secreted in the presence of natural IgM for efficient induction of specific IgG and for immune protection, identifying B-1 and B-2 cell–derived IgM antibodies as nonredundant components of the antiviral response.
Subfields: Epidemiology, Immunology
View Paper: https://www.semanticscholar.org/paper/b5985078b6b2f4b15f03eec3e2a347315c768bc4
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- Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+CD27+CD43+CD70− (2011, background): “Natural Ig is vitally important in the early defense against bacterial and viral infections (Briles et al., 1981; Boes et al., 1998; Ochsenbein et al., 1999; Baumgarth et al., 2000; Haas et al., 2005), and may play a role in a wide variety of diseases through recognition of CORRESPONDENCE Thomas L.”
- Antibody repertoire profiling with mimotope arrays (2017, background): “Natural antibodies of different isotypes have been observed to target various xeno- and autologous antigens(23-27) and carbohydrates 28 and to be an essential, non-redundant component of the host defense against viral infections.(29)”
- Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells (2008, background): “Intriguingly this protective role includes influenza virus subtypes to which mice are immunologically naı̈ve [23,24].”
- The importance of natural IgM: scavenger, protector and regulator (2010, background): “For some infections, such as with influenza virus, both natural and immune IgM are required for protectio”