Broad #hemagglutinin-specific memory B cell expansion by seasonal #influenza virus #infection reflects early-life #imprinting and #adaptation to the infecting virus (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Broad hemagglutinin-specific memory B cell expansion by seasonal influenza virus infection reflects early-life imprinting and adaptation to the infecting virus

Brenda L. Tesini, Preshetha Kanagaiah, Jiong Wang, Megan Hahn, Jessica L. Halliley, Francisco A. Chaves, Phuong Q.T. Nguyen, Aitor Nogales, Marta L. DeDiego, Christopher S. Anderson,Ali H. Ellebedy, Shirin Strohmeier, Florian Krammer, Hongmei Yang, Sanjukta Bandyopadhyay, Rafi Ahmed, John J. Treanor, Luis Martinez-Sobrido, Hana Golding, Surender Khurana,Martin S. Zand, David J. Topham, Mark Y. Sangster

DOI: 10.1128/JVI.00169-19

 

ABSTRACT

Memory B cells (MBCs) are key determinants of the B cell response to influenza virus infection and vaccination, but the effect of different forms of influenza antigen exposure on MBC populations has received little attention. We analyzed peripheral blood mononuclear cells and plasma collected following human H3N2 influenza infection to investigate the relationship between hemagglutinin-specific antibody production and changes in the size and character of hemagglutinin-reactive MBC populations. Infection produced increased concentrations of plasma IgG reactive to the H3 head of the infecting virus, to the conserved stalk, and to a broad chronological range of H3s consistent with original antigenic sin responses. H3-reactive IgG MBC expansion after infection included reactivity to head and stalk domains. Notably, expansion of H3 head-reactive MBC populations was particularly broad and reflected original antigenic sin patterns of IgG production. Findings also suggest that early-life H3N2 infection “imprints” for strong H3 stalk-specific MBC expansion. Despite the breadth of MBC expansion, the MBC response included an increase in affinity for the H3 head of the infecting virus. Overall, our findings indicate that H3-reactive MBC expansion following H3N2 infection is consistent with maintenance of response patterns established early in life, but nevertheless includes MBC adaptation to the infecting virus.

 

IMPORTANCE

Rapid and vigorous virus-specific antibody responses to influenza virus infection and vaccination result from activation of preexisting virus-specific memory B cells (MBCs). Understanding the effects of different forms of influenza virus exposure on MBC populations is therefore an important guide to the development of effective immunization strategies. We demonstrate that exposure to the influenza hemagglutinin via natural infection enhances broad protection through expansion of hemagglutinin-reactive MBC populations that recognize head and stalk regions of the molecule. Notably, we show that hemagglutinin-reactive MBC expansion reflects imprinting by early-life infection and that this might apply to stalk-reactive, as well as to head-reactive, MBCs. Our findings provide experimental support for the role of MBCs in maintaining imprinting effects and suggest a mechanism by which imprinting might confer heterosubtypic protection against avian influenza viruses. It will be important to compare our findings to the situation after influenza vaccination.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Seasonal Influenza; Avian Influenza; H3N2; Immunology.

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Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.