2025-12-09 トロント大学(U of T)
<関連情報>
- https://www.utoronto.ca/news/study-reveals-how-gut-builds-long-lasting-immunity-after-viral-infections
- https://www.cell.com/cell/abstract/S0092-8674(25)00812-8
粘膜ウイルス感染は1型濾胞性ヘルパーT細胞を介して長期にわたるIgA反応を引き起こす Mucosal viral infection elicits long-lived IgA responses via type 1 follicular helper T cells
Kei Haniuda ∙ Natalie M. Edner ∙ Yuko Makita ∙ … ∙ Gregory F. Wu ∙ Thamotharampillai Dileepan ∙ Jennifer L. Gommerman
Cell Published:November 17, 2025
DOI:https://doi.org/10.1016/j.cell.2025.07.022
Graphical abstract
Highlights
- Mucosal viral infections induce tissue-resident IgA+ long-lived plasma cells (LLPCs)
- T-bet+ IFNγ+ Type 1 TFH cells are required for virus-specific IgA+ LLPC development
- B cell Ag presentation is necessary and sufficient to induce virus-specific type 1 TFH
- An IFNγ-CXCR3 axis is required for the accumulation of IgA+ PCs at effector sites
Summary
Although immunoglobulin A (IgA)+ long-lived plasma cells (LLPCs) generated following mucosal viral infection provide durable protection against reinfection, little is known about their generation. Here, we show that rotavirus (RV) infection induces gut-resident LLPCs that produce highly mutated, protective IgA. Unlike RV-specific immunoglobulin G (IgG)+ LLPCs, IgA+ LLPCs were generated independently of major histocompatibility complex class II (MHC class II) expression by dendritic cells—rather, MHC class II on B cells was both necessary and sufficient. B cell-MHC class II was also sufficient to induce T-bet+ follicular helper T (TFH1) cells, which were crucial for RV-specific IgA+ LLPC accumulation in the gut via interferon γ (IFNγ)- and CXCR3-dependent mechanisms. Similar to RV infection, TFH1 cells were required for an influenza-specific IgA response in the airway. However, unlike RV infection, B cell-MHC class II was not sufficient to induce influenza-specific IgA+ LLPCs, suggesting the operation of mucosal-site-specific priming mechanisms. Collectively, our data reveal that unconventionally primed TFH1 cells support IgA responses to mucosal viral infections.
