SOSTDC1 for germinal center regulation T follicular helper (T FH ) cells are CD4 + T cells that facilitate B cell antibody production and B cell memory responses in the germinal centers (GCs) of lymphoid organs. These activities are in turn restrained by T follicular regulatory (T FR ) cells, a population of T cells with unclear origins. Wu et al. now demonstrate that a subpopulation of T FH cells and fibroblastic reticular cells both produce sclerostin domain-containing protein 1 (SOSTDC1), which drives T FR cell generation by inhibiting Wnt–β-catenin signaling. In mice lacking the gene Sostdc1 , T FR cell numbers were substantially decreased and GC responses were enhanced. These insights into T FR cell biology and GC regulation may have important implications for autoantibody-mediated diseases and the future development of vaccines and therapies for autoimmune disease. Science , this issue p. 984