title: The LRF transcription factor regulates mature B cell development and the germinal center response in mice.
abstract: B cells play a central role in immune system function. Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therapies for autoimmune diseases and B cell malignancies. Employing B cell-specific conditional knockout mice, we have demonstrated here that the transcription factor leukemia/lymphoma-related factor (LRF) forms an obligate dimer in B cells and regulates mature B cell lineage fate and humoral immune responses via distinctive mechanisms. Moreover, LRF inactivation in transformed B cells attenuated their growth rate. These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies.
authors.affiliation: Division of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
authors.forename: Nagisa
authors.initials: N
authors.lastname: Sakurai
authors.forename: Manami
authors.initials: M
authors.lastname: Maeda
authors.forename: Sung-Uk
authors.initials: SU
authors.lastname: Lee
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: John C
authors.initials: JC
authors.lastname: Williams
authors.forename: Lisheng
authors.initials: L
authors.lastname: Wang
authors.forename: Leila
authors.initials: L
authors.lastname: Su
authors.forename: Mai
authors.initials: M
authors.lastname: Suzuki
authors.forename: Toshiki I
authors.initials: TI
authors.lastname: Saito
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Stefano
authors.initials: S
authors.lastname: Casola
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Shinobu
authors.initials: S
authors.lastname: Tsuzuki
authors.forename: Ravi
authors.initials: R
authors.lastname: Bhatia
authors.forename: Takahiro
authors.initials: T
authors.lastname: Maeda
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C117093:Zbtb7a protein, mouse