tetano
Editor, Senior Moderator
EMBO Mol Med
. 2026 Mar 9.
doi: 10.1038/s44321-026-00395-8. Online ahead of print.
IFN-gene signatures in B cells following influenza A and B virus infection and influenza vaccination
Wuji Zhang[SUP] 1 2 [/SUP], E Kaitlynn Allen[SUP] 3 [/SUP], Shihan Li[SUP] 4 [/SUP], Ilariya Tarasova[SUP] 5 [/SUP], Rubaiyea Farrukee[SUP] 1 [/SUP], Lukasz Kedzierski[SUP] 1 [/SUP], Brad Gilbertson[SUP] 1 [/SUP], Hayley A McQuilten[SUP] 1 [/SUP], Jennifer R Habel[SUP] 1 [/SUP], Lilith F Allen[SUP] 1 [/SUP], Steven Rockman[SUP] 1 6 [/SUP], Sarah L Londrigan[SUP] 1 [/SUP], Stephen J Kent[SUP] 1 [/SUP], Adam K Wheatley[SUP] 1 [/SUP], Jason A Trubiano[SUP] 7 8 9 10 [/SUP], Tom C Kotsimbos[SUP] 11 12 [/SUP], Allen C Cheng[SUP] 13 14 [/SUP], Jan Schroeder[SUP] 4 [/SUP], Jeremy Chase Crawford[SUP] 15 [/SUP], Paul G Thomas[SUP] 16 [/SUP], Katherine Kedzierska[SUP] #[/SUP][SUP] 17 [/SUP], Thi H O Nguyen[SUP] #[/SUP][SUP] 18 [/SUP]
Affiliations
Influenza viruses continue to cause a substantial global disease burden. Despite influenza vaccination, some individuals succumb to life-threatening influenza or death. Yet our understanding of immune features elicited by vaccination and influenza A and B virus (IAV, IBV) infection is limited. To define molecular signatures of influenza-specific B-cells, we performed scRNA-sequencing of influenza-specific B-cells in vaccinees and hospitalized IAV/IBV-infected patients using HA-probes. We observed increased interferon-stimulated gene signatures (IF44L, IFITM1 and XAF1), in total B-cells from IBV-patients, but not at 1-month following patients' recovery or in IAV-patients or vaccinees. Phenotypic differentiation and isotype class-switching of HA-specific B-cells were observed following vaccination, with clonal sharing between memory and atypical B-cell phenotypes. In-vitro influenza virus infection experiments showed IBVs having higher infectivity of human PBMCs, including B-cells, and reduced B-cell proliferation compared to IAV, potentially associated with antiproliferative effect of IFITM1. We provide key insights into B-cell immunity towards IBV and IAV infections and vaccination, which will inform rational vaccine design and therapeutic strategies aimed at eliciting robust HA-specific B-cell responses, while minimizing adverse effects caused by natural infection.
Keywords: BCR; Influenza vaccination; Influenza virus infection; atypical B cells; influenza-specific B cells.
. 2026 Mar 9.
doi: 10.1038/s44321-026-00395-8. Online ahead of print.
IFN-gene signatures in B cells following influenza A and B virus infection and influenza vaccination
Wuji Zhang[SUP] 1 2 [/SUP], E Kaitlynn Allen[SUP] 3 [/SUP], Shihan Li[SUP] 4 [/SUP], Ilariya Tarasova[SUP] 5 [/SUP], Rubaiyea Farrukee[SUP] 1 [/SUP], Lukasz Kedzierski[SUP] 1 [/SUP], Brad Gilbertson[SUP] 1 [/SUP], Hayley A McQuilten[SUP] 1 [/SUP], Jennifer R Habel[SUP] 1 [/SUP], Lilith F Allen[SUP] 1 [/SUP], Steven Rockman[SUP] 1 6 [/SUP], Sarah L Londrigan[SUP] 1 [/SUP], Stephen J Kent[SUP] 1 [/SUP], Adam K Wheatley[SUP] 1 [/SUP], Jason A Trubiano[SUP] 7 8 9 10 [/SUP], Tom C Kotsimbos[SUP] 11 12 [/SUP], Allen C Cheng[SUP] 13 14 [/SUP], Jan Schroeder[SUP] 4 [/SUP], Jeremy Chase Crawford[SUP] 15 [/SUP], Paul G Thomas[SUP] 16 [/SUP], Katherine Kedzierska[SUP] #[/SUP][SUP] 17 [/SUP], Thi H O Nguyen[SUP] #[/SUP][SUP] 18 [/SUP]
Affiliations
- PMID: 41803327
- DOI: 10.1038/s44321-026-00395-8
Influenza viruses continue to cause a substantial global disease burden. Despite influenza vaccination, some individuals succumb to life-threatening influenza or death. Yet our understanding of immune features elicited by vaccination and influenza A and B virus (IAV, IBV) infection is limited. To define molecular signatures of influenza-specific B-cells, we performed scRNA-sequencing of influenza-specific B-cells in vaccinees and hospitalized IAV/IBV-infected patients using HA-probes. We observed increased interferon-stimulated gene signatures (IF44L, IFITM1 and XAF1), in total B-cells from IBV-patients, but not at 1-month following patients' recovery or in IAV-patients or vaccinees. Phenotypic differentiation and isotype class-switching of HA-specific B-cells were observed following vaccination, with clonal sharing between memory and atypical B-cell phenotypes. In-vitro influenza virus infection experiments showed IBVs having higher infectivity of human PBMCs, including B-cells, and reduced B-cell proliferation compared to IAV, potentially associated with antiproliferative effect of IFITM1. We provide key insights into B-cell immunity towards IBV and IAV infections and vaccination, which will inform rational vaccine design and therapeutic strategies aimed at eliciting robust HA-specific B-cell responses, while minimizing adverse effects caused by natural infection.
Keywords: BCR; Influenza vaccination; Influenza virus infection; atypical B cells; influenza-specific B cells.