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Current guidelines recommend vaccinations against these pathogens before or after splenectomy, but the longevity of immunity acquired after splenectomy has not been determined. The impact of splenectomy on innate immune cells is unknown. We analyzed frequency, differentiation stage, and function of innate and adaptive immunity in the peripheral blood of adult (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200941) and pediatric (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914) patients splenectomized or born asplenic and in spleens of solid organ donors. The absence of the spleen impacts the B\u2010cell compartment, causing a significant increase of circulating immature transitional and depletion of memory B cells. Using SARS\u2010CoV\u20102 vaccination as a model, we show that 1\u2009year after the last immunization, despite normal levels of neutralizing antibodies, memory B and T cells were significantly reduced. Analysis of post\u2010pandemic spleens shows that spike\u2010specific memory B and T cells homed to the spleen. We also show a previously unrecognized role of the spleen in the homeostasis of innate NK and V\u03b42 T cells. These populations showed altered phenotype and impaired function in the adults, but not in children, suggesting that other tissues may support innate cell development during early life. The reduced function of innate lymphocytes must be considered as an additional immune impairment and risk factor. These findings emphasize the spleen's irreplaceable role in maintaining immune memory across all ages and suggest that its absence contributes to dysfunctions of innate and adaptive immunity in adults.\n                  <\/jats:p>","DOI":"10.1002\/ajh.27634","type":"journal-article","created":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T06:20:21Z","timestamp":1739600421000},"page":"770-784","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Impairment of Innate Immunity and Depletion of Vaccine\u2010Induced Memory B and T Cells in the Absence\u00a0of\u00a0the Spleen"],"prefix":"10.1002","volume":"100","author":[{"given":"Veronica","family":"Bordoni","sequence":"first","affiliation":[{"name":"Department of Hematology\/Oncology, Cell and Gene Therapy Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Laura","family":"Cinicola","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome  Rome Italy"},{"name":"Pediatric Unit, NESMOS Department, Sant'Andrea University Hospital Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Piano Mortari","sequence":"additional","affiliation":[{"name":"Research Area of Immunology, B\u2010Cell Lab Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Castilletti","sequence":"additional","affiliation":[{"name":"Department of Infectious\u2010Tropical Diseases and Microbiology IRCCS Sacro Cuore Don Calabria Hospital  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Guarracino","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Cell and Gene Therapy Bambino Ges\u00f9 Children's 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