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We investigated the effect of controlled human malaria infection (CHMI) on B cell phenotypes in individuals with different Pf immunity status: malaria-na\u00efve, immunized with PfSPZ-CVac and semi-immune (lifelong-exposed) volunteers. Compared to na\u00efve, semi-immune but not vaccinated individuals, had increased baseline frequencies of immature B cells (CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD10\n                    <jats:sup>+<\/jats:sup>\n                    ), active naive (IgD\n                    <jats:sup>+<\/jats:sup>\n                    CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD21\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) B cells, active atypical (IgD\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD21\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) memory B cells (MBCs), active classical (IgD\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD27\n                    <jats:sup>+<\/jats:sup>\n                    CD21\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) MBCs and CD1c\n                    <jats:sup>+<\/jats:sup>\n                    -B cells but lower frequencies of some IgG\n                    <jats:sup>+<\/jats:sup>\n                    -B cells. The frequencies of CD1c\n                    <jats:sup>+<\/jats:sup>\n                    active atypical MBCs correlated positively with anti-Pf antibodies and negatively with circulating eotaxin levels, while the opposite was observed for IgG\n                    <jats:sup>+<\/jats:sup>\n                    resting atypical MBCs. During early blood-stage infection (day 11 after CHMI), there was an expansion of resting classical (IgD\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD27\n                    <jats:sup>+<\/jats:sup>\n                    CD21\n                    <jats:sup>+<\/jats:sup>\n                    ) MBCs in all three groups. Vaccination, compared to placebo, altered the effect of CHMI on B cells, showing a positive association with resting classical MBCs (\u03b2\u2009=\u20090.190, 95% CI 0.011\u20130.368) and active na\u00efve-PD1\n                    <jats:sup>+<\/jats:sup>\n                    (\u03b2\u2009=\u20090.637, 95% CI 0.058 to 1.217) frequencies, and a negative one with CD1c\n                    <jats:sup>+<\/jats:sup>\n                    resting atypical MBCs (\u03b2\u2009=\u2009\u2212\u20090.328, 95% CI \u2212\u20090.621 to \u2212\u20090.032). In addition, the sickle cell trait in semi-immune subjects altered the effect of CHMI on several B cells. In conclusion, lifelong but not vaccine exposure to malaria was associated with increased frequencies of multiple B cell subsets, with higher and lower percentages of CD1c and IgG expressing-cells, respectively. A single infection (CHMI) induces changes in B cell frequencies and is modulated by sickle cell trait and malaria-immunity status.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Clinical Trials Registration<\/jats:italic>\n                    NCT01624961, NCT02115516, and NCT02237586.\n                  <\/jats:p>","DOI":"10.1007\/s00430-025-00847-x","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T04:37:43Z","timestamp":1758947863000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of controlled human Plasmodium falciparum infection on B cell subsets in individuals with different levels of malaria immunity"],"prefix":"10.1007","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2298-4085","authenticated-orcid":false,"given":"Pilar","family":"Requena","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria Patricia","family":"G\u00f3mez-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B. 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