title: Bob1 limits cellular frequency of T-follicular helper cells.
abstract: T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B-cell lymphoma-6 and Blimp-1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique mechanisms to establish Tfh-cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1. Bob1 of Tfh cells was dispensable for the expression of B-cell lymphoma-6 and the functional property of the cells for B cell help. However, upon initial immunization of foreign antigens, the percentages of Tfh cells in Bob1(-/-) mice were much higher than those in wild-type (WT) mice. In addition, expansion of Tfh cells within Bob1(-/-) CD4(+) T cells transferred into WT mice revealed that the high frequency of Tfh cells was caused by a T-cell-intrinsic mechanism. These findings were further supported by the results of in vitro studies demonstrating that Bob1(-/-) Tfh cells had greater proliferative activity in response to stimuli by CD3/CD28 monoclonal antibody and were also refractory to CD3-induced cell death in comparison to WT Tfh cells. These results suggest that Tfh cells harbor a Bob1-related mechanism to restrict numerical frequency against stimulation of TCRs.
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawata
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumiya
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kamekura
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Sumito
authors.initials: S
authors.lastname: Jitsukawa
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nagaya
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ogasawara
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takano
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Division of Pathology and Laboratory Medicine, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Shigehara
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Himi
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Ichimiya
keywords: Apoptosis; Bob1; Cellular proliferation; T-follicular helper cells