{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:25:40Z","timestamp":1789097140819,"version":"build-2803163510"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/CRTF\/20\/24035"],"award-info":[{"award-number":["FS\/CRTF\/20\/24035"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Intermediate Basic Science Fellowship","award":["FS\/20\/23\/34784"],"award-info":[{"award-number":["FS\/20\/23\/34784"]}]},{"name":"BHF Project Grants","award":["PG\/17\/73\/33251"],"award-info":[{"award-number":["PG\/17\/73\/33251"]}]},{"name":"BHF Project Grants","award":["PG\/22\/10898"],"award-info":[{"award-number":["PG\/22\/10898"]}]},{"name":"BHF Chair of Cardiovascular Medicine","award":["G101517"],"award-info":[{"award-number":["G101517"]}]},{"DOI":"10.13039\/501100001674","name":"Leducq Foundation","doi-asserted-by":"publisher","award":["G107743"],"award-info":[{"award-number":["G107743"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"H2020","doi-asserted-by":"publisher","award":["G106938"],"award-info":[{"award-number":["G106938"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["211100\/Z\/18\/Z"],"award-info":[{"award-number":["211100\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The adaptive immune response plays an important role in atherosclerosis. In response to a high-fat\/high-cholesterol (HF\/HC) diet, marginal zone B (MZB) cells activate an atheroprotective programme by regulating the differentiation and accumulation of \u2018poorly differentiated\u2019 T follicular helper (Tfh) cells. On the other hand, Tfh cells activate the germinal centre response, which promotes atherosclerosis through the production of class-switched high-affinity antibodies. We therefore investigated the direct role of Tfh cells and the role of IL18 in Tfh differentiation in atherosclerosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We generated atherosclerotic mouse models with selective genetic deletion of Tfh cells, MZB cells, or IL18 signalling in Tfh cells. Surprisingly, mice lacking Tfh cells had increased atherosclerosis. Lack of Tfh not only reduced class-switched IgG antibodies against oxidation-specific epitopes (OSEs) but also reduced atheroprotective natural IgM-type anti-phosphorylcholine (PC) antibodies, despite no alteration of natural B1 cells. Moreover, the absence of Tfh cells was associated with an accumulation of MZB cells with substantially reduced ability to secrete antibodies. In the same manner, MZB cell deficiency in Ldlr\u2212\/\u2212 mice was associated with a significant decrease in atheroprotective IgM antibodies, including natural anti-PC IgM antibodies. In humans, we found a positive correlation between circulating MZB-like cells and anti-OSE IgM antibodies. Finally, we identified an important role for IL18 signalling in HF\/HC diet\u2013induced Tfh.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings reveal a previously unsuspected role of MZB cells in regulating atheroprotective \u2018natural\u2019 IgM antibody production in a Tfh-dependent manner, which could have important pathophysiological and therapeutic implications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvae027","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T07:33:27Z","timestamp":1706081607000},"page":"318-328","source":"Crossref","is-referenced-by-count":30,"title":["Marginal zone B cells produce \u2018natural\u2019 atheroprotective IgM antibodies in a T cell\u2013dependent 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