Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions |
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| Authors: | Chung Yeonseok Tanaka Shinya Chu Fuliang Nurieva Roza I Martinez Gustavo J Rawal Seema Wang Yi-Hong Lim Hoyong Reynolds Joseph M Zhou Xiao-hui Fan Hui-min Liu Zhong-ming Neelapu Sattva S Dong Chen |
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| Institution: | Department of Immunology, Center for Cancer Immunology Research, The University of Texas-MD Anderson Cancer Center, Houston, Texas, USA. yeonseok.chung@uth.tmc.edu |
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| Abstract: | Foxp3(+) regulatory T (T(reg)) cells suppress different types of immune responses to help maintain homeostasis in the body. How T(reg) cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T(reg) cells expressing CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression of CXCR5 on T(reg) cells depends on Bcl-6. These CXCR5(+)Bcl-6(+) T(reg) cells are absent in the thymus but can be generated de novo from CXCR5(-)Foxp3(+) natural T(reg) precursors. A lack of CXCR5(+) T(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(reg) cells that drives the development of follicular regulatory T (T(FR)) cells that function to inhibit the germinal center reactions. |
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