title: The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help.
abstract: Germinal center (GC) B cells cycle between two states, the light zone (LZ) and the dark zone (DZ), and in the latter they proliferate and hypermutate their immunoglobulin genes. How this functional transition takes place is still controversial. In this study, we demonstrate that ablation of Foxo1 after GC development led to the loss of the DZ GC B cells and disruption of the GC architecture, which is consistent with recent studies. Mechanistically, even upon provision of adequate T cell help, Foxo1-deficient GC B cells showed less proliferative expansion than controls. Moreover, we found that the transcription factor BATF was transiently induced in LZ GC B cells in a Foxo1-dependent manner and that deletion of BATF similarly led to GC disruption. Thus, our results are consistent with a model where the switch from the LZ to the DZ is triggered after receipt of T cell help, and suggest that Foxo1-mediated BATF up-regulation is at least partly involved in this switch.
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.|Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Shinnakasu
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ise
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Kawai
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Takeshi
authors.identifier: 0000-0001-7489-1051
authors.initials: T
authors.lastname: Egawa
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan kurosaki@ifrec.osaka-u.ac.jp.|Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Tomohiro
authors.identifier: 0000-0002-6352-304X
authors.initials: T
authors.lastname: Kurosaki
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D000071161:Forkhead Box Protein O1 / Q000502:physiology*; D018858:Germinal Center / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse