Cutting Edge: IL-21 and TLR Signaling Regulate Germinal Center Responses in a B Cell-Intrinsic Manner

IL-21 produced by follicular Th (Tfh) cells is an important regulator of Tfh cell development and B cell responses, including germinal center (GC) formation. However, whether defective GC formation and Ab responses are a consequence of impaired Tfh cells development or a B cell-intrinsic defect in IL-21–deficient mice requires clarification. To address this question, we generated chimeric mice lacking IL-21R exclusively on B cells. In this study, we demonstrate that GC reaction and B cell responses induced by immunization with virus-like particles were strongly reduced in both global and B cell-specific IL-21R–deficient mice. Interestingly, the presence of TLR7 ligand within virus-like particles largely restored defective GC reaction and Ab responses in global as well as in B cell-specific IL-21R–deficient mice. Hence, IL-21 acts directly on B cells and cooperates with TLR signaling for optimal B cell responses.