{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T04:12:27Z","timestamp":1774584747075,"version":"3.50.1"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012505","name":"Royal Perth Hospital Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The diversity of B cell subsets and their contribution to vaccine-induced immunity in humans are not well elucidated but hold important implications for rational vaccine design. Prior studies demonstrate that B cell subsets distinguished by immunoglobulin (Ig) isotype expression exhibit divergent activation-induced fates. Here, the antigen-specific B cell response to tetanus toxoid (TTd) booster vaccination was examined in healthy adults, using a dual-TTd tetramer staining flow cytometry protocol. Unsupervised analyses of the data revealed that prior to vaccination, IgM-expressing CD27<jats:sup>+<\/jats:sup> B cells accounted for the majority of TTd-binding B cells. 7 days following vaccination, there was an acute expansion of TTd-binding plasmablasts (PB) predominantly expressing IgG, and a minority expressing IgA or IgM. Frequencies of all PB subsets returned to baseline at days 14 and 21. TTd-binding IgG<jats:sup>+<\/jats:sup> and IgA<jats:sup>+<\/jats:sup> memory B cells (MBC) exhibited a steady and delayed maximal expansion compared to PB, peaking in frequencies at day 14. In contrast, the number of TTd-binding IgM<jats:sup>+<\/jats:sup>IgD<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> B cells and IgM-only CD27<jats:sup>+<\/jats:sup> B cells remain unchanged following vaccination. To examine TTd-binding capacity of IgG<jats:sup>+<\/jats:sup> MBC and IgM<jats:sup>+<\/jats:sup>IgD<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> B cells, surface TTd-tetramer was normalised to expression of the B cell receptor-associated CD79b subunit. CD79b-normalised TTd binding increased in IgG<jats:sup>+<\/jats:sup> MBC, but remained unchanged in IgM<jats:sup>+<\/jats:sup>IgD<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> B cells, and correlated with the functional affinity index of plasma TTd-specific IgG antibodies, following vaccination. Finally, frequencies of activated (PD-1<jats:sup>+<\/jats:sup>ICOS<jats:sup>+<\/jats:sup>) circulating follicular helper T cells (cT<jats:sub>FH<\/jats:sub>), particularly of the CXCR3<jats:sup>-<\/jats:sup>CCR6<jats:sup>-<\/jats:sup> cT<jats:sub>FH<\/jats:sub>2 cell phenotype, at their peak expansion, strongly predicted antigen-binding capacity of IgG<jats:sup>+<\/jats:sup> MBC. These data highlight the phenotypic and functional diversity of the B cell memory compartment, in their temporal kinetics, antigen-binding capacities and association with cT<jats:sub>FH<\/jats:sub> cells, and are important parameters for consideration in assessing vaccine-induced immune responses.<\/jats:p>","DOI":"10.3389\/fimmu.2021.738123","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T06:16:53Z","timestamp":1632809813000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Characterising the Phenotypic Diversity of Antigen-Specific Memory B Cells Before and After Vaccination"],"prefix":"10.3389","volume":"12","author":[{"given":"M. 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