{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:33:35Z","timestamp":1781703215108,"version":"3.54.5"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In the present study, we aimed at identifying the mechanisms whereby the vitamin A metabolite all-trans retinoic acid (RA) promotes the formation of plasma cells upon stimulation of B cells via the innate immunity receptors TLR9 and RP105. Most often, differentiation of B cells involves the sequential events of class switch recombination and somatic hypermutations characteristic of germinal center reactions, followed by plasma cell formation. By studying the regulatory networks known to drive these reactions, we revealed that RA enhances the expression of the plasma cell\u2013generating transcription factors IFN regulatory factor (IRF)4 and Blimp1, and paradoxically also activation-induced deaminase (AID) involved in somatic hypermutations\/class switch recombination, in primary human B cells. IRF4 was identified as a particularly important protein involved in the RA-mediated production of IgG in TLR9\/RP105-stimulated B cells. Based on kinetic studies, we present a model suggesting that the initial induction of IRF4 by RA favors AID expression. According to this model, the higher level of IRF4 that eventually arises results in sustained elevated levels of Blimp1. Regarded as a master regulator of plasma cell development, Blimp1 will in turn suppress AID expression and drive the formation of IgG-secreting plasma cells. Notably, we demonstrated IRF4 to be deregulated in B cells from common variable immunodeficiency patients, contributing to the observed aberrant expression of AID in these patients. Taken together, the present study both provides new insight into the mechanisms whereby RA induces differentiation of B cells and identifies IRF4 as a key to understand the defective functions of B cells in common variable immunodeficiency patients.<\/jats:p>","DOI":"10.4049\/jimmunol.1500250","type":"journal-article","created":{"date-parts":[[2015,8,15]],"date-time":"2015-08-15T02:49:15Z","timestamp":1439606955000},"page":"2601-2611","source":"Crossref","is-referenced-by-count":26,"title":["IRF4 Is a Critical Gene in Retinoic Acid\u2013Mediated Plasma Cell Formation and Is Deregulated in Common Variable Immunodeficiency\u2013Derived B Cells"],"prefix":"10.1093","volume":"195","author":[{"given":"Randi L","family":"Indrev\u00e6r","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo , N-0317 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan \u00d8","family":"Moskaug","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo , N-0317 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingvild","family":"Paur","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Oslo , N-0317 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siv K","family":"B\u00f8hn","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Oslo , N-0317 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silje F","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine, Oslo University Hospital, University of Oslo , N-0424 Oslo ,","place":["Norway"]},{"name":"Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, University of Oslo , N-0424 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rune","family":"Blomhoff","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Oslo , N-0317 Oslo ,","place":["Norway"]},{"name":"Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital , N-0424 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e5l","family":"Aukrust","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine, Oslo University Hospital, University of Oslo , N-0424 Oslo ,","place":["Norway"]},{"name":"Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, University of Oslo , N-0424 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00f8rre","family":"Fevang","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine, Oslo University Hospital, University of Oslo , N-0424 Oslo ,","place":["Norway"]},{"name":"Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, University of Oslo , N-0424 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi K","family":"Blomhoff","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo , N-0317 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,15]]},"reference":[{"key":"2025030704124954600_r1","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1111\/j.1753-4887.1998.tb01643.x","article-title":"The role of vitamin A and related retinoids in immune function","volume":"56","author":"Semba","year":"1998","journal-title":"Nutr. 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