IL-21 lowers the B cell receptor affinity threshold for participation in a T cell dependent immune response.

The expansion of antigen-specific T and B cells and generation of germinal centers (GC) are prerequisites for long-lasting, high-affinity antibody-mediated immune protection. Affinity for antigen is fundamental to GC B cell recruitment as it determines access to T cell help and thus competitiveness within the response. However, how T-cell derived signals contribute to such recruitment is incompletely understood. Here we report how the signature cytokine of follicular helper T cells, IL-21, acts as a key regulator of the initial B cell response. By activating AKT and S6, IL-21 accelerates cell cycle progression and the rate of cycle entry of B cells, increasing their contribution to the ensuing GC. This effect is most pronounced on B cells receiving weak T cell co-stimulation in vitro and on low-affinity B cells in vivo, which require IL-21 receptor signaling for their recruitment and persistence in the early response. Thus, IL-21 determines the composition of the T-dependent B cell response by regulating the breadth of BCR affinities that can participate. ### Competing Interest Statement The authors have declared no competing interest.