Abstract
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.
Highlights
B cell memory generated by influenza A virus (IAV) infection and vaccination consists of antibodies (Abs) and memory B cells (MBCs)
Our goal in this review is to combine observations from human and animal studies to provide a picture of the HA-specific B cell response to IAV infection in adults
Preexisting MBC activation generates cells that along with activated naïve B cells, seed germinal centers (GCs) for generation of MBCs and plasma cells adapted to variant/novel HA epitopes. This process involves another form of B cell competition, the competition between GC B cells for antigen held by follicular dendritic cells (FDCs); acquisition of this antigen is a prerequisite for positive selection
Summary
B cell memory generated by influenza A virus (IAV) infection and vaccination consists of antibodies (Abs) and memory B cells (MBCs). Our goal is to review the Ab response to IAV infection in immune adults with an emphasis on the contribution of MBCs. We consider only IgG-expressing MBCs and focus entirely on the B cell response to the viral HA, the viral attachment protein that initiates cell infection by binding to sialylated receptors [6]. We consider only IgG-expressing MBCs and focus entirely on the B cell response to the viral HA, the viral attachment protein that initiates cell infection by binding to sialylated receptors [6] This enables us to consider the Pathogens 2019, 8, 167; doi:10.3390/pathogens8040167 www.mdpi.com/journal/pathogens. Where appropriate, we incorporate findings from animal models that assist us to develop a more complete picture of processes in responding lymphoid tissues
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