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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 re-enter 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 antistem 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 toward 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.<\/jats:p>","DOI":"10.1093\/intimm\/dxag003","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T12:29:27Z","timestamp":1768307367000},"page":"383-395","source":"Crossref","is-referenced-by-count":2,"title":["T-cell help is a limiting factor for rare anti-influenza memory B cells to re-enter germinal centers and generate potent broadly neutralizing antibodies"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9359-7190","authenticated-orcid":false,"given":"Yang","family":"Xue","sequence":"first","affiliation":[{"name":"Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]},{"name":"Graduate School of Frontier Biosciences, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Tai","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]},{"name":"Regulation of Host Defense Team, Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Mori","sequence":"additional","affiliation":[{"name":"Regulation of Host Defense Team, Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Sakai","sequence":"additional","affiliation":[{"name":"Research Division, Chugai Pharmaceutical Co. 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