{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T06:11:48Z","timestamp":1777961508853,"version":"3.51.4"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Early-life vaccinations often yield short-lived antibody (Ab) responses due to limited germinal center (GC) reaction and plasma cell (PC) survival. The aim of the study was to assess how vaccine delivery routes (homologous versus heterologous) in mice shape early-life GC dynamics and outputs. 14 days post-booster immunization, spleen, cervical (CLN), and inguinal (ILN) lymph nodes were analyzed for GC B cells, T follicular helper (T\n                    <jats:sub>FH<\/jats:sub>\n                    ) and regulatory (T\n                    <jats:sub>FR<\/jats:sub>\n                    ) cells, and GC-derived memory B cells and expression of B cell activating factor receptor (BAFF-R)\/transmembrane activator and cyclophilin ligand interactor (TACI) on GC and memory B cells. Plasmablast\/PC and their B cell maturation antigen (BCMA) expression, vaccine-specific Ab-secreting cells (ASCs), and serum and salivary Abs were also assessed. We observed that the booster route determined the anatomical site of the GC responses. Homologous subcutaneous (s.c.)\/s.c. immunization increased GC induction in spleen and s.c. draining LNs, the ILNs, whereas s.c.\/intranasal (i.n.) immunization primarily induced GCs in mucosal draining LNs, the CLNs. The memory B cell composition was also route-dependent, with s.c.\/i.n. immunization preferentially generating GC-derived IgM\n                    <jats:sup>+<\/jats:sup>\n                    memory B cells across lymphoid tissues. In contrast, homologous s.c.\/s.c. immunization promoted PC differentiation in spleen, yielding more BCMA\n                    <jats:sup>+<\/jats:sup>\n                    cells especially in ILNs and BM, associated with elevated vaccine-specific serum IgG (days 7-14) and increased IgG ASCs in spleen and bone marrow. Heterologous s.c.\/i.n. immunization instead favored PC differentiation only in the CLNs and elevated serum and salivary IgA Abs. Correspondingly, BAFF-R and TACI expression was elevated on splenic GC B cells following s.c.\/s.c. immunization, whereas a higher expression was observed on CLNs GC B cells and IgM\n                    <jats:sup>+<\/jats:sup>\n                    GC-derived memory cells after s.c.\/i.n. immunization. Together, these findings demonstrate that the booster immunization route directs the anatomical site of GC activity and determines the dominant GC-derived memory B cell subset. Homologous s.c.\/s.c. immunization maximizes systemic IgG responses, through enhanced BCMA-associated PC survival, whereas s.c.\/i.n. immunization promotes IgM\n                    <jats:sup>+<\/jats:sup>\n                    GC-derived memory B cell induction while confining PC differentiation and BCMA expression to CLNs, resulting in combined systemic and mucosal Ab responses. These results support rational, route-informed early-life vaccine design to selectively enhance systemic IgG or combined systemic\u2013mucosal antibody responses.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1792155","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:32:24Z","timestamp":1777959144000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Parenteral neonatal priming followed by heterologous mucosal booster favors IgM+ memory B cell induction over systemic plasma cell differentiation"],"prefix":"10.3389","volume":"17","author":[{"given":"Poorya","family":"Foroutan Pajoohian","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Biomedical Center, School of Health Sciences, University of Iceland","place":["Reykjavik, Iceland"]},{"name":"Department of Immunology, Landspitali, The National University Hospital of Iceland","place":["Reykjavik, Iceland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audur Anna","family":"Aradottir Pind","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biomedical Center, School of Health Sciences, University of Iceland","place":["Reykjavik, Iceland"]},{"name":"Department of Immunology, Landspitali, The National University Hospital of Iceland","place":["Reykjavik, Iceland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny Lorena","family":"Molina Estupi\u00f1an","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biomedical Center, School of Health Sciences, University of Iceland","place":["Reykjavik, Iceland"]},{"name":"Department of Immunology, Landspitali, The National University Hospital of Iceland","place":["Reykjavik, Iceland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Christensen","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, Statens Serum Institut","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel Kristian","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, Statens Serum Institut","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorunn A.","family":"Olafsdottir","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biomedical Center, School of Health Sciences, University of Iceland","place":["Reykjavik, Iceland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingileif","family":"Jonsdottir","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biomedical Center, School of Health Sciences, University of Iceland","place":["Reykjavik, Iceland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania P.","family":"Bjarnarson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biomedical Center, School of Health Sciences, University of Iceland","place":["Reykjavik, Iceland"]},{"name":"Department of Immunology, Landspitali, The National University Hospital of Iceland","place":["Reykjavik, Iceland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(24)00850-x","article-title":"Contribution of vaccination to improved survival and health: modelling 50 years of the expanded programme on immunization","volume":"403","author":"Shattock","year":"2024","journal-title":"Lancet (Lond Engl)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2508","article-title":"B-cell responses to vaccination at the extremes of age","volume":"9","author":"Siegrist","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218011","article-title":"CD4 T helper cell subsets and related human immunological disorders","volume":"21","author":"Zhu","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.2.556","article-title":"Cellular interaction in germinal centers. 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