T follicular regulatory cells in the regulation of B cell responses

• Tfh cells promote the germinal center reaction and antibody production.
• Tfr cells control the germinal reaction by suppressing Tfh cells and B cells.
• Tfr cells are found in many tissues and can respond to both foreign and self antigens.
• Altered Tfr:Tfh cell ratios correlate with autoimmune disease.

High affinity antibodies result from interactions between B cells and T follicular helper (Tfh) cells in germinal centers (GCs). Recent studies have identified an effector subset of T regulatory cells termed T follicular regulatory (Tfr) cells that specifically controls GC responses by suppressing Tfh and B cells. The discovery of Tfr cells has shed new light on pathways regulating humoral immunity that enable potent and specific responses to pathogens while restricting autoimmunity. Here, we review the current understanding of the cellular and molecular mechanisms underlying the differentiation and function of Tfr cells. In this context we discuss recent insights into the role of Tfh cells in disease, how this knowledge may be translated therapeutically, and important areas of further research.