Stat3 Is Important for Follicular Regulatory T Cell Differentiation

The production of antibody is precisely controlled during the germinal center (GC) reaction. This process is dependent on the help from follicular T helper (Tfh) cells to germinal center (GC) B cells and is regulated by regulatory follicular T helper (Tfr) cells. How Tfr cells develop and how their suppressive activity functions are not well understood. Here, we found that Stat3 is indispensible for Tfr cell differentiation. After immunization with Sheep Red Blood Cells (SRBC), the loss of Tfr cells caused by deletion of Stat3 in Treg cells does not affect the size of Tfh or GC B cell population, but rather leads to strongly enhanced production of antigen-specific IgG1 and IgG2b. In Peyer's patches (PPs) in the gut, we found that Stat3 expression in Treg cells is also required for Tfr cell formation to commensal organisms. However, loss of Tfr cells in the gut did not affect the numbers of Tfh cells and GC B cells, nor affect IgG1 or IgA switching by GC B cells. Overall, our study has uncovered unique roles of Stat3 in Tfr cell differentiation and the regulation of the antibody response.