{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:35:53Z","timestamp":1791275753997,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2014,4,22]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Atherosclerotic lesions grow via the accumulation of leukocytes and oxidized lipoproteins in the vessel wall. Leukocytes can attenuate or augment atherosclerosis through the release of cytokines, chemokines, and other mediators. Deciphering how leukocytes develop, oppose, and complement each other\u2019s function and shape the course of disease can illuminate our understanding of atherosclerosis. Innate response activator (IRA) B cells are a recently described population of granulocyte macrophage colony-stimulating factor\u2013secreting cells of hitherto unknown function in atherosclerosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>Here, we show that IRA B cells arise during atherosclerosis in mice and humans. In response to a high-cholesterol diet, IRA B cell numbers increase preferentially in secondary lymphoid organs via Myd88-dependent signaling. Mixed chimeric mice lacking B cell\u2013derived granulocyte macrophage colony-stimulating factor develop smaller lesions with fewer macrophages and effector T cells. Mechanistically, IRA B cells promote the expansion of classic dendritic cells, which then generate interferon \u03b3\u2013producing T helper-1 cells. This IRA B cell\u2013dependent T helper-1 skewing manifests in an IgG1-to-IgG2c isotype switch in the immunoglobulin response against oxidized lipoproteins.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Granulocyte macrophage colony-stimulating factor\u2013producing IRA B cells alter adaptive immune processes and shift the leukocyte response toward a T helper-1\u2013associated milieu that aggravates atherosclerosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.113.006381","type":"journal-article","created":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T05:38:48Z","timestamp":1391233128000},"page":"1677-1687","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":135,"title":["Innate Response Activator B Cells Aggravate Atherosclerosis by Stimulating T Helper-1 Adaptive Immunity"],"prefix":"10.1161","volume":"129","author":[{"given":"Ingo","family":"Hilgendorf","sequence":"first","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Theurl","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa M.S.","family":"Gerhardt","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clinton S.","family":"Robbins","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg F.","family":"Weber","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayelet","family":"Gonen","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Degousee","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health 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(I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Zirlik","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, 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F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdish","family":"Butany","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., 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Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Libby","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., 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