Follicular regulatory T cells expressing foxp3 and Bcl-6 suppress germinal center reactions

[Foxp3.sup.+] regulatory T ([T.sub.reg]) cells suppress different types of immune responses to help maintain homeostasis in the body. How [T.sub.reg] cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of [T.sub.reg] cells expressing CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression of CXCR5 on [T.sub.reg] cells depends on Bcl-6. These [CXCR5.sup.+][Bcl-6.sup.+] [T.sub.reg] cells are absent in the thymus but can be generated de novo from CXCR5-[Foxp3.sup.+] natural [T.sub.reg] precursors. A lack of CXCR5+ [T.sub.reg] cells leads to greater germinal center reactions including germinal center B cells, affinity maturation of antibodies and the differentiation of plasma cells. These results unveil a Bcl-6-CXCR5 axis in [T.sub.reg] cells that drives the development of follicular regulatory T ([T.sub.FR]) cells that function to inhibit the germinal center reactions.
The vertebrate immune system contains a unique subset of T cells expressing Foxp3 that prevent autoimmunity against self antigens and exaggerated immune responses. Deficiency of Foxp3 in humans results in [...]