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These studies have been thwarted by the rarity of IgE<jats:sup>+<\/jats:sup> cells <jats:italic>in\u00a0vivo<\/jats:italic> and the low frequency of class switch recombination (<jats:styled-content style=\"fixed-case\">CSR<\/jats:styled-content>) to IgE <jats:italic>ex\u00a0vivo<\/jats:italic>. To determine the main source of IgE<jats:sup>+<\/jats:sup> cells, we investigated the relation between the phenotypic composition of tonsil B cells and the <jats:styled-content style=\"fixed-case\">CSR<\/jats:styled-content> to IgE <jats:italic>ex\u00a0vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human tonsil B cells were analyzed by flow cytometry (<jats:styled-content style=\"fixed-case\">FACS<\/jats:styled-content>) and cultured with <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 and anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40 to induce <jats:styled-content style=\"fixed-case\">CSR<\/jats:styled-content> to IgE. Na\u00efve, germinal center (GC), early GC (eGC), and memory tonsil B cells were isolated by <jats:styled-content style=\"fixed-case\">FACS<\/jats:styled-content>, and their capacities for <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 and anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40 signaling, cell proliferation, and <jats:italic>de novo<\/jats:italic> class switching to IgE were analyzed by <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">FACS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>B cells from different tonsils exhibited varying capacities for <jats:styled-content style=\"fixed-case\">CSR<\/jats:styled-content> to IgE <jats:italic>ex\u00a0vivo<\/jats:italic>. This was correlated with the percentage of <jats:styled-content style=\"fixed-case\">eGC<\/jats:styled-content> B cells in the tonsil at the outset of the culture. Despite relatively poor cell viability, <jats:styled-content style=\"fixed-case\">eGC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content> B\u2010cell cultures produced the highest yields of IgE<jats:sup>+<\/jats:sup> cells compared to na\u00efve and memory B\u2010cell cultures. The main factors accounting for this result were the strength of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104R and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40 signaling and relative rates of cell proliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study shows that the maturation state of tonsil B cells determines their capacity to undergo class switching to IgE <jats:italic>ex\u00a0vivo<\/jats:italic>, with the <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\u2010derived B cells yielding the highest percentage of IgE<jats:sup>+<\/jats:sup> cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.12679","type":"journal-article","created":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T08:23:35Z","timestamp":1435220615000},"page":"1269-1277","source":"Crossref","is-referenced-by-count":24,"title":["Intrinsic properties of germinal center\u2010derived B cells promote their enhanced class switching to IgE"],"prefix":"10.1111","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8228-4868","authenticated-orcid":false,"given":"F.","family":"Ramadani","sequence":"first","affiliation":[{"name":"Randall Division of Cell and Molecular Biohphysics King's College London London UK"},{"name":"Medical Research Council and Asthma UK Centre Allergic Mechanisms in Asthma London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Upton","sequence":"additional","affiliation":[{"name":"Randall Division of Cell and Molecular Biohphysics King's College London London UK"},{"name":"Medical Research Council and Asthma UK Centre Allergic Mechanisms in Asthma London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Hobson","sequence":"additional","affiliation":[{"name":"Division of Asthma, Allergy and Lung Biology King's College London London UK"},{"name":"Medical Research Council and Asthma UK Centre Allergic Mechanisms in Asthma London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.\u2010C.","family":"Chan","sequence":"additional","affiliation":[{"name":"Randall Division of Cell and Molecular Biohphysics King's College London London UK"},{"name":"Medical Research Council and Asthma UK Centre Allergic Mechanisms in Asthma London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Mzinza","sequence":"additional","affiliation":[{"name":"Randall Division of Cell and Molecular Biohphysics King's College London London UK"},{"name":"Medical Research Council and Asthma UK Centre Allergic Mechanisms in Asthma London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Bowen","sequence":"additional","affiliation":[{"name":"Randall Division of Cell and Molecular Biohphysics King's College London London UK"},{"name":"Medical Research Council and Asthma UK Centre Allergic Mechanisms in Asthma London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Kerridge","sequence":"additional","affiliation":[{"name":"Randall Division of Cell and Molecular Biohphysics King's College London London UK"},{"name":"Medical Research Council and Asthma UK Centre Allergic Mechanisms in Asthma London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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