Suppression by T cells leads to durable and selective inhibition of B cell effector function.

Follicular regulatory T cells (T cells) inhibit follicular helper T cell (T cell)-mediated antibody production. The mechanisms by which T cells exert their key immunoregulatory functions are largely unknown. Here we found that T cells induced a distinct suppressive state in T cells and B cells, in which effector transcriptional signatures were maintained but key effector molecules and metabolic pathways were suppressed. The suppression of B cell antibody production and metabolism by T cells was durable and persisted even in the absence of T cells. This durable suppression was due in part to epigenetic changes. The cytokine IL-21 was able to overcome T cell-mediated suppression and inhibited T cells and stimulated B cells. By determining mechanisms of T cell-mediated suppression, we have identified methods for modulating the function of T cells and antibody production.