title: Essential role of EBF1 in the generation and function of distinct mature B cell types.
abstract: The transcription factor EBF1 is essential for lineage specification in early B cell development. In this study, we demonstrate by conditional mutagenesis that EBF1 is required for B cell commitment, pro-B cell development, and subsequent transition to the pre-B cell stage. Later in B cell development, EBF1 was essential for the generation and maintenance of several mature B cell types. Marginal zone and B-1 B cells were lost, whereas follicular (FO) and germinal center (GC) B cells were reduced in the absence of EBF1. Activation of the B cell receptor resulted in impaired intracellular signaling, proliferation and survival of EBF1-deficient FO B cells. Immune responses were severely reduced upon Ebf1 inactivation, as GCs were formed but not maintained. ChIP- and RNA-sequencing of FO B cells identified EBF1-activated genes that encode receptors, signal transducers, and transcriptional regulators implicated in B cell signaling. Notably, ectopic expression of EBF1 efficiently induced the development of B-1 cells at the expense of conventional B cells. These gain- and loss-of-function analyses uncovered novel important functions of EBF1 in controlling B cell immunity.
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
authors.forename: Bojan
authors.initials: B
authors.lastname: Vilagos
authors.forename: Mareike
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Abdallah
authors.initials: A
authors.lastname: Souabni
authors.forename: Qiong
authors.initials: Q
authors.lastname: Sun
authors.forename: Barbara
authors.initials: B
authors.lastname: Werner
authors.forename: Jasna
authors.initials: J
authors.lastname: Medvedovic
authors.forename: Ivan
authors.initials: I
authors.lastname: Bilic
authors.forename: Martina
authors.initials: M
authors.lastname: Minnich
authors.forename: Elin
authors.initials: E
authors.lastname: Axelsson
authors.forename: Markus
authors.initials: M
authors.lastname: Jaritz
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D051757:PAX5 Transcription Factor / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D017455:Receptors, IgE / Q000032:analysis; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*
chemical_list: C081976:EBF1 protein, human; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D015534:Trans-Activators