Suppression by TFR\ cells leads to durable and selective inhibition of B cell effector function

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