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Here, we show that Casp6 regulates early B\u2010cell development. One\u2010week\u2010old Casp6 knockout (Casp6 <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) mice have significantly more splenic B\u2010cell subsets than wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) mice. Adult Casp6 <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice have normal levels of total splenic B cells but have increased numbers of B1a B cells and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>43<jats:sup>+<\/jats:sup> \u201ctransitional\u201d or splenic red pulp (<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>) B cells. These results suggested that Casp6 may function to control B\u2010cell numbers under nonhomeostatic conditions and during B\u2010cell development. Consistent with this model, reconstitution of B cells was dysregulated in Casp6 <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice after sublethal irradiation. Furthermore, bone marrow pro\u2010B, pre\u2010B and immature B\u2010cell numbers were significantly higher in 1\u2010week\u2010old Casp6 <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice than in 1\u2010week\u2010old <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice. Casp6 <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> pro\u2010B cells proliferated more in response to <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20107 than <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> pro\u2010B cells, suggesting that Casp6 regulates early B\u2010cell responses to <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20107. Indeed, adult and aged Casp6 <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice had elevated numbers of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20107\u03b1R<jats:sup>+<\/jats:sup>Sca1<jats:sup>+<\/jats:sup> precursors of common lymphoid progenitors, suggesting Casp6 may help regulate progenitors of B cells and early B\u2010lineage cells. Casp6 regulates B\u2010cell programs both during early development and after antigen stimulation in the periphery.<\/jats:p>","DOI":"10.1111\/imcb.12172","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T16:21:59Z","timestamp":1528129319000},"page":"1072-1082","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Regulation of B\u2010lineage cells by caspase 6"],"prefix":"10.1111","volume":"96","author":[{"given":"Chie","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Immunology University of Washington Seattle WA 98109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine L","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Washington Seattle WA 98109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia 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