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Role of Memory B Cells in Hemagglutinin-Specific Antibody Production Following Human Influenza A Virus Infection

David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
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Pathogens 2019, 8(4), 167; https://doi.org/10.3390/pathogens8040167
Received: 23 August 2019 / Revised: 25 September 2019 / Accepted: 26 September 2019 / Published: 28 September 2019
(This article belongs to the Special Issue Influenza Virus and Vaccination)
When influenza A virus infects an immune individual, preexisting memory B cell (MBC) activation and rapid anamnestic antibody production plays a key role in viral clearance. The most effective neutralizing antibodies target the antigenically variable head of the viral hemagglutinin (HA); antibodies against the conserved HA stalk provide broader but less potent protection. In this review, we provide a comprehensive picture of an adult’s HA-specific antibody response to influenza virus infection. The process is followed from preexisting HA-specific MBC activation and rapid production of anti-HA antibodies, through to germinal center seeding and adaptation of the response to novel features of the HA. A major focus of the review is the role of competition between preexisting MBCs in determining the character of the HA-reactive antibody response. HA novelty modifies this competition and can shift the response from the immunodominant head to the stalk. We suggest that antibodies resulting from preexisting MBC activation are important regulators of anti-HA antibody production and play a role in positive selection of germinal center B cells reactive to novel HA epitopes. Our review also considers the role of MBCs in the effects of early-life imprinting on HA head- and stalk-specific antibody responses to influenza infection. An understanding of the processes described in this review will guide development of vaccination strategies that provide broadly effective protection. View Full-Text
Keywords: influenza A virus; infection; hemagglutinin; hemagglutin stalk; memory B cells; antibodies; germinal centers; original antigenic sin; imprinting influenza A virus; infection; hemagglutinin; hemagglutin stalk; memory B cells; antibodies; germinal centers; original antigenic sin; imprinting
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MDPI and ACS Style

Sangster, M.Y.; Nguyen, P.Q.T.; Topham, D.J. Role of Memory B Cells in Hemagglutinin-Specific Antibody Production Following Human Influenza A Virus Infection. Pathogens 2019, 8, 167.

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