Influenza virus infection expands the breadth of antibody responses through IL-4 signalling in B cells

Kosuke Miyauchi, Yu Adachi, Keisuke Tonouchi, Taiki Yajima, Yasuyo Harada, Hidehiro Fukuyama, Senka Deno, Yoichiro Iwakura, Akihiko Yoshimura, Hideki Hasegawa, Katsuyuki Yugi, Shin ichiro Fujii, Osamu Ohara, Yoshimasa Takahashi, Masato Kubo

Research output: Contribution to journalArticlepeer-review

Abstract

Influenza viruses are a major public health problem. Vaccines are the best available countermeasure to induce effective immunity against infection with seasonal influenza viruses; however, the breadth of antibody responses in infection versus vaccination is quite different. Here, we show that nasal infection controls two sequential processes to induce neutralizing IgG antibodies recognizing the hemagglutinin (HA) of heterotypic strains. The first is viral replication in the lung, which facilitates exposure of shared epitopes that are otherwise hidden from the immune system. The second process is the germinal center (GC) response, in particular, IL-4 derived from follicular helper T cells has an essential role in the expansion of rare GC-B cells recognizing the shared epitopes. Therefore, the combination of exposure of the shared epitopes and efficient proliferation of GC-B cells is critical for generating broadly-protective antibodies. These observations provide insight into mechanisms promoting broad protection from virus infection.

Original languageEnglish
Article number3789
JournalNature communications
Volume12
Issue number1
DOIs
Publication statusPublished - 2021 Dec

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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