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However, Tfr\u2010cell function in the GC is not well understood. Here, we define Tfr cells as a CD4<jats:sup>+<\/jats:sup> Foxp3<jats:sup>+<\/jats:sup> CXCR5<jats:sup>hi<\/jats:sup> PD\u20101<jats:sup>hi<\/jats:sup> CD25<jats:sup>low<\/jats:sup> TIGIT<jats:sup>high<\/jats:sup> T\u2010cell population. Furthermore, we have used a novel mouse model (\u201cBcl6FC\u201d) to delete the Bcl6 gene in Foxp3<jats:sup>+<\/jats:sup> T\u00a0cells and thus specifically deplete Tfr cells. Following immunization, Bcl6FC mice develop normal Tfh\u2010 and GCB\u2010cell populations. However, Bcl6FC mice produce altered antigen\u2010specific antibody responses, with reduced titers of IgG and significantly increased IgA. Bcl6FC mice also developed IgG antibodies with significantly decreased avidity to antigen in an HIV\u20101 gp120 \u201cprime\u2010boost\u201d vaccine model. In an autoimmune lupus model, we observed strongly elevated anti\u2010DNA IgA titers in Bcl6FC mice. Additionally, Tfh cells from Bcl6FC mice consistently produce higher levels of Interferon\u2010\u03b3, IL\u201010 and IL\u201021. Loss of Tfr cells therefore leads to highly abnormal Tfh\u2010cell and GCB\u2010cell responses. Overall, our study has uncovered unique regulatory roles for Tfr cells in the GC response.<\/jats:p>","DOI":"10.1002\/eji.201546094","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T12:07:40Z","timestamp":1455797260000},"page":"1152-1161","source":"Crossref","is-referenced-by-count":168,"title":["Follicular regulatory T\u00a0cells repress cytokine production by follicular helper T\u00a0cells and optimize IgG responses in mice"],"prefix":"10.1002","volume":"46","author":[{"given":"Hao","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Indiana University School of Medicine  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Massachusetts Medical School  Worcester MA 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