IL-21R signaling at the level of Th cells is required to induce optimal B-cell help function. (A) Top panels: WT T cells were activated in the presence (right panel) or absence of IL-6 (left panel) and tested for ThB function in the presence of B cells purified from control or IL-21R^−/− mice. Bottom panels: WT or IL-21R–deficient T cells were tested for helping activity toward WT syngeneic B cells. (B) CD62L⁺CD4⁺ T cells were stimulated in the presence or absence of recombinant IL-21 or IL-6 cytokines (20 ng/mL). Recovered cells were rested 1 day in fresh medium and tested for B-cell help capacity. Results are expressed of mean plus or minus SD of triplicate cultures and are representative of 2 (A) or 3 (B) independent experiments.