{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:05:53Z","timestamp":1767179153931,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013663","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000}}],"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-162268"],"award-info":[{"award-number":["PJT-162268"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Manitoba, Graduate Student Fellowship"},{"name":"Children\u2019s Guild Association Endowed Chair in Pediatric Immunology (to D.J.R), the Hansen Investigator in Pediatric Innovation Endowment"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Phosphatidylinositol 3-kinase delta (PI3KCD) is a critical signaling enzyme for B cell development, activation, function and immune regulation. Gain-of-function mutations in PI3KCD result in the congenital immunodeficiency known as Activated PI3KCD Syndrome (APDS). APDS patients are prone to repeated infections and other serious clinical manifestations. Here, we determine how B cell-intrinsic expression of the APDS-associated PI3KCD\n                    <jats:sup>E1021K<\/jats:sup>\n                    mutation impacts immune responses\u00a0to the protozoan parasite\n                    <jats:italic>\n                      <jats:italic>Trypanosoma congolense<\/jats:italic>\n                    <\/jats:italic>\n                    . PI3KCD\n                    <jats:sup>E1021K\/B<\/jats:sup>\n                    mice exhibit a significant expansion of IL10-expressing\u2009B cells within the spleen and peritoneal cavity, which was associated with impaired control of\n                    <jats:italic>\n                      <jats:italic>T. congolense<\/jats:italic>\n                    <\/jats:italic>\n                    infection. Despite the generation of robust germinal center, plasma cell and antibody responses, PI3KCD\n                    <jats:sup>E1021K\/B<\/jats:sup>\n                    mice show elevation in the first wave of parasitemia and increased mortality. We further characterize the phenotype of the expanded IL10-producing B cell population in PI3KCD\n                    <jats:sup>E1021K\/B<\/jats:sup>\n                    mice, which show hallmarks of innate-like regulatory B cells (Breg) and expression of multiple inhibitory molecules. This Breg expansion is associated with reduced IFN\u03b3\/IL10 ratio, reduced TNF\u03b1 production and impaired activation of myeloid cells, likely compromising the innate response to infection. These findings highlight the profound impact of dysregulated PI3KCD activity on regulatory B cells that can functionally impair innate immune responses controlling a systemic parasite protozoan disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013663","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T18:40:04Z","timestamp":1762368004000},"page":"e1013663","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["PI3Kdelta-driven expansion of regulatory B cells impairs protective immune responses to Trypanosoma congolense parasite infection"],"prefix":"10.1371","volume":"21","author":[{"given":"Folayemi","family":"Olayinka-Adefemi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sen","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milad","family":"Sabzevary-ghahfarokhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle N.","family":"Wray-Dutra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Rawlings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jude","family":"Uzonna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1175-5498","authenticated-orcid":true,"given":"Aaron J.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"ppat.1013663.ref001","doi-asserted-by":"crossref","first-page":"652405","DOI":"10.3389\/fped.2021.652405","article-title":"Activated PI3Kinase Delta Syndrome\u2014A Multifaceted Disease","volume":"9","author":"R Thouenon","year":"2021","journal-title":"Front Pediatr"},{"key":"ppat.1013663.ref002","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3389\/fimmu.2018.00369","article-title":"Activated PI3 kinase delta syndrome: from genetics to 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