tetano
Editor, Senior Moderator
Int Immunol
. 2026 Jan 16:dxag003.
doi: 10.1093/intimm/dxag003. Online ahead of print.
T cell help is a limiting factor for rare anti-influenza memory B cells to reenter germinal centers and generate potent broadly neutralizing antibodies
Yang Xue[SUP] 1 2 [/SUP], Yuki Tai[SUP] 1 3 [/SUP], Hiromi Yamamoto[SUP] 1 [/SUP], Daiki Mori[SUP] 3 [/SUP], Kaori Sakai[SUP] 4 [/SUP], Takuya Miyazaki[SUP] 4 [/SUP], Mikito Owa[SUP] 4 [/SUP], Kohei Kometani[SUP] 5 [/SUP], Isao Ebina[SUP] 4 6 [/SUP], Ryusuke Omiya[SUP] 4 6 [/SUP], Kunihiro Hattori[SUP] 4 6 [/SUP], Takeshi Inoue[SUP] 1 7 8 [/SUP], Wataru Ise[SUP] 3 [/SUP], Ryo Shinnakasu[SUP] 9 [/SUP], Tomohiro Kurosaki[SUP] 1 2 [/SUP]
Affiliations
Development of vaccines eliciting broadly neutralizing influenza antibodies (bnAbs) is an extraordinary challenge. One hypothetical proposal is that CD4+ T cell help to rare immuno-subdominant bnAb class memory B cells is one critical factor to cause these B cells to reenter secondary germinal centers (GCs) and generate potent bnAbs. In this regard, we previously showed that the prototypic hemagglutinin stem vaccine does not contain the dominant CD4+ T cell epitope. Here, to test the above hypothesis, we examined the effects of adding a single influenza T cell epitope to the stem vaccine in an influenza pre-infected booster mouse model. We found that this fused booster vaccine efficiently recruited anti-stem memory B cells with prior GC experience into the secondary GCs in draining lymph nodes. Furthermore, these secondary GC-experienced cells evolved, thereby contributing to generation of more potent neutralizing activity towards variant viruses. Thus, our results suggest the importance of T cell help in generating potent bnAbs by recruiting rare subdominant memory B cells into secondary GCs, and have implications for vaccine design.
Keywords: antibody maturation; follicular helper T cells.
. 2026 Jan 16:dxag003.
doi: 10.1093/intimm/dxag003. Online ahead of print.
T cell help is a limiting factor for rare anti-influenza memory B cells to reenter germinal centers and generate potent broadly neutralizing antibodies
Yang Xue[SUP] 1 2 [/SUP], Yuki Tai[SUP] 1 3 [/SUP], Hiromi Yamamoto[SUP] 1 [/SUP], Daiki Mori[SUP] 3 [/SUP], Kaori Sakai[SUP] 4 [/SUP], Takuya Miyazaki[SUP] 4 [/SUP], Mikito Owa[SUP] 4 [/SUP], Kohei Kometani[SUP] 5 [/SUP], Isao Ebina[SUP] 4 6 [/SUP], Ryusuke Omiya[SUP] 4 6 [/SUP], Kunihiro Hattori[SUP] 4 6 [/SUP], Takeshi Inoue[SUP] 1 7 8 [/SUP], Wataru Ise[SUP] 3 [/SUP], Ryo Shinnakasu[SUP] 9 [/SUP], Tomohiro Kurosaki[SUP] 1 2 [/SUP]
Affiliations
- PMID: 41540896
- DOI: 10.1093/intimm/dxag003
Development of vaccines eliciting broadly neutralizing influenza antibodies (bnAbs) is an extraordinary challenge. One hypothetical proposal is that CD4+ T cell help to rare immuno-subdominant bnAb class memory B cells is one critical factor to cause these B cells to reenter secondary germinal centers (GCs) and generate potent bnAbs. In this regard, we previously showed that the prototypic hemagglutinin stem vaccine does not contain the dominant CD4+ T cell epitope. Here, to test the above hypothesis, we examined the effects of adding a single influenza T cell epitope to the stem vaccine in an influenza pre-infected booster mouse model. We found that this fused booster vaccine efficiently recruited anti-stem memory B cells with prior GC experience into the secondary GCs in draining lymph nodes. Furthermore, these secondary GC-experienced cells evolved, thereby contributing to generation of more potent neutralizing activity towards variant viruses. Thus, our results suggest the importance of T cell help in generating potent bnAbs by recruiting rare subdominant memory B cells into secondary GCs, and have implications for vaccine design.
Keywords: antibody maturation; follicular helper T cells.