Germinal centers (GC) are the sites of B cell clonal expansion, somatic hypermutation and clonal selection, a process that leads to the production of antibodies of higher affinity [1](#ref-0001). Efforts have been made to understand the kinetic of events controlling the GC and the production of specific antibodies in protective as well in pathogenic responses, such as autoimmunity and allergy. The ability of newly mutated GC clones to capture and present antigen to T follicular helper cells (Tfh) in the light zone of the GC is crucial for clonal survival and selection. Tfh cells produce IL-21, a key cytokine for the GC reaction and antibody responses [2](#ref-0002). However, it was not understood how IL-21 acts independently on T and B cells to mediate the GC reaction. In this study Quast and colleagues [3](#ref-0003) contribute to elucidate the specific role of IL-21 on the GC reaction and how IL-21 bioavailability affects the outcome of the GC response. They demonstrate that IL-21 influences Tfh cell differentiation and expansion early, before the GC establishment, as well later during GC development, through both autocrine and paracrine mechanisms, regardless of cognate T-B cell interactions.