Wu, HaoChen, YuxinLiu, HongXu, Lin-LinTeuscher, PaulaWang, ShixiaLu, ShanDent, Alexander L.2017-08-032017-08-032016-05Wu, H., Chen, Y., Liu, H., Xu, L.-L., Teuscher, P., Wang, S., … Dent, A. L. (2016). Follicular regulatory T cells repress cytokine production by follicular helper T cells and optimize IgG responses in mice. European Journal of Immunology, 46(5), 1152–1161. http://doi.org/10.1002/eji.201546094https://hdl.handle.net/1805/13741Follicular helper T (Tfh) cells provide crucial help to germinal center B (GCB) cells for proper antibody production, and a specialized subset of regulatory T cells, follicular regulatory T (Tfr) cells, modulate this process. However, Tfr-cell function in the GC is not well understood. Here, we define Tfr cells as a CD4(+) Foxp3(+) CXCR5(hi) PD-1(hi) CD25(low) TIGIT(high) T-cell population. Furthermore, we have used a novel mouse model ("Bcl6FC") to delete the Bcl6 gene in Foxp3(+) T cells and thus specifically deplete Tfr cells. Following immunization, Bcl6FC mice develop normal Tfh- and GCB-cell populations. However, Bcl6FC mice produce altered antigen-specific 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-1 gp120 "prime-boost" vaccine model. In an autoimmune lupus model, we observed strongly elevated anti-DNA IgA titers in Bcl6FC mice. Additionally, Tfh cells from Bcl6FC mice consistently produce higher levels of Interferon-γ, IL-10 and IL-21. Loss of Tfr cells therefore leads to highly abnormal Tfh-cell and GCB-cell responses. Overall, our study has uncovered unique regulatory roles for Tfr cells in the GC response.en-USPublisher PolicyGerminal center responseFollicular T cellsRegulatory T cellsAntibodyBcl6Article