Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions

Y Chung, S Tanaka, F Chu, RI Nurieva, GJ Martinez… - Nature medicine, 2011 - nature.com
Y Chung, S Tanaka, F Chu, RI Nurieva, GJ Martinez, S Rawal, YH Wang, H Lim…
Nature medicine, 2011nature.com
Abstract Foxp3+ regulatory T (Treg) cells suppress different types of immune responses to
help maintain homeostasis in the body. How Treg cells regulate humoral immunity, including
germinal center reactions, is unclear. Here we identify a subset of Treg cells expressing
CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression
of CXCR5 on Treg cells depends on Bcl-6. These CXCR5+ Bcl-6+ Treg cells are absent in
the thymus but can be generated de novo from CXCR5− Foxp3+ natural Treg precursors. A …
Abstract
Foxp3+ regulatory T (Treg) cells suppress different types of immune responses to help maintain homeostasis in the body. How Treg cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of Treg cells expressing CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression of CXCR5 on Treg cells depends on Bcl-6. These CXCR5+Bcl-6+ Treg cells are absent in the thymus but can be generated de novo from CXCR5Foxp3+ natural Treg precursors. A lack of CXCR5+ Treg 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 Treg cells that drives the development of follicular regulatory T (TFR) cells that function to inhibit the germinal center reactions.
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