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IL-21 has pleiotropic functions, including induction of Th17 T cells, inhibition of Treg development, and modulation of antibody responses of B lymphocytes. Genetic polymorphisms of IL21 have been associated to poor pregnancy outcomes. However, the mechanism of IL-21 actions needs further evaluation. Here, we postulate that IL-21 affects splenic B cell function during pregnancy and shapes immune responses. We show that splenic B cells from CBA\/J\u2009\u00d7\u2009BALB\/c mice with favorable pregnancy outcome expressed lower IL21R levels than in CBA\/J\u2009\u00d7\u2009DBA\/2J mice, a mouse model for immune-induced bad pregnancy outcome. As a consequence, B cells from CBA\/J\u2009\u00d7\u2009BALB\/c mice reacted less sensitively to IL-21 than B cells from non-pregnant mice (NPM) or from CBA\/J\u2009\u00d7\u2009DBA\/2J mice. Also, LPS-induced apoptotic rates were altered in NPM and CBA\/J\u2009\u00d7\u2009DBA\/2J but not in CBA\/J\u2009\u00d7\u2009BALB\/c mice. This is accompanied by improved survival of B cells that produce the anti-inflammatory cytokine IL-10 upon stimulation with LPS. We also observed lower numbers of CD4+CXCR5+Bcl-6+ follicular T-helper cells (Tfh) in normal pregnant mice, compared to non-pregnant and mice with disturbed pregnancies. Our data indicate that alterations of the Tfh\/IL-21\/IL-10 axis may have important influence on pregnancy outcome.<\/jats:p>","DOI":"10.1530\/rep-19-0407","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T11:43:37Z","timestamp":1580125417000},"page":"351-359","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":12,"title":["Pregnancy status alters IL-21-mediated effects on murine B lymphocytes"],"prefix":"10.1093","volume":"159","author":[{"given":"Carolin","family":"Fr\u00f6hlich","sequence":"first","affiliation":[{"name":"Research Laboratories , Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Ehrhardt","sequence":"additional","affiliation":[{"name":"Research Laboratories , Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Research Laboratories , Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominika","family":"Trojnarska","sequence":"additional","affiliation":[{"name":"Research Laboratories , Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marek","family":"Zygmunt","sequence":"additional","affiliation":[{"name":"Research Laboratories , Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dami\u00e1n Oscar","family":"Muzzio","sequence":"additional","affiliation":[{"name":"Research Laboratories , Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,3,1]]},"reference":[{"key":"2026010712215447500_bib1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.3389\/fimmu.2017.00319","article-title":"The other function: class II-restricted antigen presentation by B cells","author":"Adler","year":"2017","journal-title":"Frontiers in Immunology"},{"key":"2026010712215447500_bib2","doi-asserted-by":"publisher","first-page":"e13663","DOI":"10.1371\/journal.pone.0013663","article-title":"A new mouse model to explore therapies for preeclampsia","author":"Ahmed","year":"2010","journal-title":"PLoS ONE"},{"key":"2026010712215447500_bib3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4049\/jimmunol.167.1.1","article-title":"Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex","author":"Asao","year":"2001","journal-title":"Journal of Immunology"},{"key":"2026010712215447500_bib4","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1073\/pnas.0807309106","article-title":"A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice","author":"Bubier","year":"2009","journal-title":"PNAS"},{"key":"2026010712215447500_bib5","doi-asserted-by":"publisher","first-page":"4261","DOI":"10.4049\/jimmunol.175.5.3447-d","article-title":"IL-10 prevents naturally occurring fetal loss in the CBA x DBA\/2 mating combination, and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of IFN-tau","author":"Chaouat","year":"1995","journal-title":"Journal of Immunology"},{"key":"2026010712215447500_bib6","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3389\/fimmu.2014.00253","article-title":"Regulation of the anti-inflammatory cytokines interleukin-4 and interleukin-10 during pregnancy","author":"Chatterjee","year":"2014","journal-title":"Frontiers in Immunology"},{"key":"2026010712215447500_bib7","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1111\/aji.12329","article-title":"Interleukin-10: a pleiotropic regulator in pregnancy","author":"Cheng","year":"2015","journal-title":"American Journal of Reproductive Immunology"},{"key":"2026010712215447500_bib12","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/0008-8749(80)90404-9","article-title":"Impairment of host-versus-graft reaction in pregnant mice. 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