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We now show that Itch directly limits B cell activity. While Itch-deficient mice displayed normal numbers of preimmune B cell populations, they showed elevated numbers of antigen-experienced B cells. Mixed bone marrow chimeras revealed that Itch acts within B cells to limit naive and, to a greater extent, germinal center (GC) B cell numbers. B cells lacking Itch exhibited increased proliferation, glycolytic capacity, and mTORC1 activation. Moreover, stimulation of these cells in vivo by WT T cells resulted in elevated numbers of GC B cells, PCs, and serum IgG. These results support a novel role for Itch in limiting B cell metabolism and proliferation to suppress antigen-driven B cell responses.<\/jats:p>","DOI":"10.1084\/jem.20181953","type":"journal-article","created":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T18:44:04Z","timestamp":1563302644000},"page":"2170-2183","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["The E3 ubiquitin ligase Itch restricts antigen-driven B cell responses"],"prefix":"10.1084","volume":"216","author":[{"given":"Emily K.","family":"Moser","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, Philadelphia, PA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Roof","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Dybas","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, Philadelphia, PA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn A.","family":"Spruce","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, Philadelphia, PA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H.","family":"Seeholzer","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, Philadelphia, PA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Cancro","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0455-3767","authenticated-orcid":true,"given":"Paula M.","family":"Oliver","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, Philadelphia, PA 1"},{"name":"University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2019,7,16]]},"reference":[{"key":"2023072822254669000_bib1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/imr.12301","article-title":"The E3 ligase Itch in immune regulation and beyond","volume":"266","author":"Aki","year":"2015","journal-title":"Immunol. 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