title: Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity.
abstract: The transcription factor Bcl6 is essential for the development of germinal center (GC) B cells and follicular helper T (Tfh) cells. However, little is known about in vivo dynamics of Bcl6 protein expression during and after development of these cells. By using a Bcl6 reporter mouse strain, we found that antigen-engaged B cells upregulated Bcl6 before clustering in GCs. Two-photon microscopic analysis indicated that Bcl6 upregulation in pre-GC B cells contributed to sustaining their interactions with helper T cells and was required for their entry to GC clusters. Our data also suggested that Tfh cells gradually downmodulated Bcl6 protein over weeks after development. The Bcl6-low Tfh cells rapidly terminated proliferation and upregulated IL-7 receptor. These results clarify the role of Bcl6 in pre-GC B cell dynamics and highlight the modulation of Bcl6 expression in Tfh cells that persist in the late phase of the antibody response.
authors.affiliation: Research Unit for Immunodynamics, RIKEN, Research Center for Allergy and Immunology, Yokohama, 230-0045, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitano
authors.forename: Saya
authors.initials: S
authors.lastname: Moriyama
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ando
authors.forename: Masaki
authors.initials: M
authors.lastname: Hikida
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Takaharu
authors.initials: T
authors.lastname: Okada
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D010641:Phenotype; D051560:Proto-Oncogene Proteins c-bcl-6; D020395:Receptors, Interleukin-7 / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D000941:Antigens; C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D020395:Receptors, Interleukin-7