title: Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells.
abstract: The transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into the functions of Ebf1 at distinct stages of differentiation, we conditionally inactivated Ebf1. We found that Ebf1 is required for the proliferation, survival, and signaling of pro-B cells and peripheral B-cell subsets, including B1 cells and marginal zone B cells. The proliferation defect of Ebf1-deficient pro-B cells and the impaired expression of multiple cell cycle regulators are overcome by transformation with v-Abl. The survival defect of transformed Ebf1(fl/fl) pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-x(L). In mature B cells, Ebf1 deficiency interferes with signaling via the B-cell-activating factor receptor (BAFF-R)- and B-cell receptor (BCR)-dependent Akt pathways. Moreover, Ebf1 is required for germinal center formation and class switch recombination. Genome-wide analyses of Ebf1-mediated gene expression and chromatin binding indicate that Ebf1 regulates both common and distinct sets of genes in early and late stage B cells. By regulating important components of transcription factor and signaling networks, Ebf1 appears to be involved in the coordination of cell proliferation, survival, and differentiation at multiple stages of B lymphopoiesis.
authors.affiliation: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Györy
authors.forename: Sören
authors.initials: S
authors.lastname: Boller
authors.forename: Robert
authors.initials: R
authors.lastname: Nechanitzky
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mandel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pott
authors.forename: Edison
authors.initials: E
authors.lastname: Liu
authors.forename: Rudolf
authors.initials: R
authors.lastname: Grosschedl
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C489921:Ebf1 protein, mouse; D007143:Immunoglobulin Heavy Chains; D015534:Trans-Activators