title: Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions.
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.
authors.affiliation: Department of Immunology, Center for Cancer Immunology Research, The University of Texas-MD Anderson Cancer Center, Houston, Texas, USA. yeonseok.chung@uth.tmc.edu
authors.forename: Yeonseok
authors.initials: Y
authors.lastname: Chung
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Fuliang
authors.initials: F
authors.lastname: Chu
authors.forename: Roza I
authors.initials: RI
authors.lastname: Nurieva
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Martinez
authors.forename: Seema
authors.initials: S
authors.lastname: Rawal
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Wang
authors.forename: Hoyong
authors.initials: H
authors.lastname: Lim
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Reynolds
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Zhou
authors.forename: Hui-min
authors.initials: HM
authors.lastname: Fan
authors.forename: Zhong-ming
authors.initials: ZM
authors.lastname: Liu
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014066:Palatine Tonsil / Q000276:immunology / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5 / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
chemical_list: C084103:BCL6 protein, human; C095085:CXCR5 protein, human; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5