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We have previously reported that <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> mice display an increased percentage of <jats:styled-content style=\"fixed-case\">TACI<\/jats:styled-content><jats:sup>high<\/jats:sup>\u2010expressing B cells compared with C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice and this trait is linked to chromosomes 1 and 8. In this paper the genetic association of the transmembrane activator, calcium modulator and cyclophilin ligand interactor (<jats:styled-content style=\"fixed-case\">TACI<\/jats:styled-content>) trait was confirmed using double congenic <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>.<jats:italic>B6C1\/Idd22<\/jats:italic> mice. <jats:styled-content style=\"fixed-case\">TACI<\/jats:styled-content> ligation by a proliferation\u2010inducing ligand (<jats:styled-content style=\"fixed-case\">APRIL<\/jats:styled-content>) has been shown to influence plasma cell differentiation, immunoglobulin production and isotype switch. Hence, the functional consequence of the up\u2010regulation of <jats:styled-content style=\"fixed-case\">TACI<\/jats:styled-content> on <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> B cells was analysed both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> B cells stimulated with <jats:styled-content style=\"fixed-case\">APRIL<\/jats:styled-content> showed an enhanced plasma cell differentiation and class switch to IgG and IgA compared with B cells from C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice. Moreover, flow cytometry analyses revealed that germinal centre B cells in <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> failed to down\u2010regulate <jats:styled-content style=\"fixed-case\">TACI<\/jats:styled-content>. Availability of the <jats:styled-content style=\"fixed-case\">TACI<\/jats:styled-content> ligand B\u2010cell activating factor (<jats:styled-content style=\"fixed-case\">BAFF<\/jats:styled-content>) has been shown to be a limiting factor in the germinal centre reaction. In line with this, upon immunization with 4\u2010hydroxy\u20103\u2010nitrophenylacetyl hapten\u2010conjugated hen egg lysozyme, <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> mice produced higher titres of low\u2010affinity antibodies compared with C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice. This observation was supported by the detection of increased levels of <jats:styled-content style=\"fixed-case\">BAFF<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> germinal centres after immunization compared with C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 by immunofluorescence. Our results support the hypothesis that increased <jats:styled-content style=\"fixed-case\">TACI<\/jats:styled-content> expression on <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> B cells contributes to the pathogenesis of type 1 diabetes in the <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> mouse.<\/jats:p>","DOI":"10.1111\/imm.12651","type":"journal-article","created":{"date-parts":[[2016,7,22]],"date-time":"2016-07-22T06:53:19Z","timestamp":1469170399000},"page":"297-305","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Increased expression of <scp>TACI<\/scp> on <scp>NOD<\/scp> B cells results in germinal centre reaction anomalies, enhanced plasma cell differentiation and immunoglobulin production"],"prefix":"10.1111","volume":"149","author":[{"given":"Viqar S.","family":"Banday","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology Division 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