tetano
Editor, Senior Moderator
Int Immunol
. 2020 Jun 6;dxaa038.
doi: 10.1093/intimm/dxaa038. Online ahead of print.
Stereotyped B-cell Response That Counteracts Antigenic Variation of Influenza Viruses
Keisuke Tonouchi[SUP] 1 2 [/SUP], Yu Adachi[SUP] 1 [/SUP], Saya Moriyama[SUP] 1 [/SUP], Kaori Sano[SUP] 3 [/SUP], Koshiro Tabata[SUP] 3 [/SUP], Keigo Ide[SUP] 2 4 [/SUP], Haruko Takeyama[SUP] 2 4 5 6 [/SUP], Tadaki Suzuki[SUP] 3 [/SUP], Yoshimasa Takahashi[SUP] 1 [/SUP]
Affiliations
Abstract
Influenza A subtypes are categorized into group 1 and group 2 based on hemagglutinin (HA) sequence. Owing to the phylogenetic distance of HAs in different groups, antibodies that bind multiple HA subtypes across different groups are extremely rare. In this study, we demonstrated that an immunization with acid-treated HA antigen elicits germinal center (GC) B cells that bind multiple HA subtypes in both group 1 and group 2. The cross-group GC B cells utilized mostly one VH gene (1S56) and exhibited a sign of clonal evolution within GCs. The 1S56-lineage IgGs derived from GC B cells were able to bind to HA protein on infected cell surface but not to native form of HA protein, suggesting the cryptic nature of 1S56 epitope and its exposure in infected cells. Finally, the 1S56-lineage IgGs provided protection against lethal infection in Fc-dependent manner, independent of the virus neutralizing activity. Thus, we identified 1S56-lineage antibodies as unique stereotype for achieving cross-group influenza specificity. The antigens exposing the 1S56 epitope may be good candidates for broadly protective immunogens.
Keywords: B cells; germinal center; influenza vaccine; non-neutralizing antibodies.
. 2020 Jun 6;dxaa038.
doi: 10.1093/intimm/dxaa038. Online ahead of print.
Stereotyped B-cell Response That Counteracts Antigenic Variation of Influenza Viruses
Keisuke Tonouchi[SUP] 1 2 [/SUP], Yu Adachi[SUP] 1 [/SUP], Saya Moriyama[SUP] 1 [/SUP], Kaori Sano[SUP] 3 [/SUP], Koshiro Tabata[SUP] 3 [/SUP], Keigo Ide[SUP] 2 4 [/SUP], Haruko Takeyama[SUP] 2 4 5 6 [/SUP], Tadaki Suzuki[SUP] 3 [/SUP], Yoshimasa Takahashi[SUP] 1 [/SUP]
Affiliations
- PMID: 32504541
- DOI: 10.1093/intimm/dxaa038
Abstract
Influenza A subtypes are categorized into group 1 and group 2 based on hemagglutinin (HA) sequence. Owing to the phylogenetic distance of HAs in different groups, antibodies that bind multiple HA subtypes across different groups are extremely rare. In this study, we demonstrated that an immunization with acid-treated HA antigen elicits germinal center (GC) B cells that bind multiple HA subtypes in both group 1 and group 2. The cross-group GC B cells utilized mostly one VH gene (1S56) and exhibited a sign of clonal evolution within GCs. The 1S56-lineage IgGs derived from GC B cells were able to bind to HA protein on infected cell surface but not to native form of HA protein, suggesting the cryptic nature of 1S56 epitope and its exposure in infected cells. Finally, the 1S56-lineage IgGs provided protection against lethal infection in Fc-dependent manner, independent of the virus neutralizing activity. Thus, we identified 1S56-lineage antibodies as unique stereotype for achieving cross-group influenza specificity. The antigens exposing the 1S56 epitope may be good candidates for broadly protective immunogens.
Keywords: B cells; germinal center; influenza vaccine; non-neutralizing antibodies.