title: Establishment and maintenance of B cell identity.
abstract: B lymphocyte differentiation is dependent on an intricate interplay of transcription factors and signaling pathways to establish a lineage-specific program of gene expression. Functional perturbations of several transcription factors by gain- or loss-of-function experiments indicated that E2A, EBF1, and FoxO1 are required for the specification of the B cell lineage, whereas Pax5 antagonizes alternative cell fates by repressing genes that allow for responsiveness to T lymphoid- and myeloid-promoting signals. However, genome-wide analysis of EBF1-binding sites and their functional interrogation indicated that EBF1 is involved in both activation of the B cell program and repression of alternative cell fates. Recent studies indicate that EBF1 function is required throughout the B cell lineage until the onset of plasma cell differentiation and includes a role in the maintenance of B cell identity. Thus, early B cell differentiation requires intertwined networks of transcription factors in which EBF1 collaborates with E2A and FoxO1 to activate the B lineage program and acts together with Pax5 to antagonize alternative cell fates.
authors.affiliation: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany grosschedl@ie-freiburg.mpg.de.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Grosschedl
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology*; D001665:Binding Sites; D002454:Cell Differentiation; D019070:Cell Lineage; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology; D015534:Trans-Activators / Q000378:metabolism; D058127:Transcription Factor 3 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C081976:EBF1 protein, human; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D015534:Trans-Activators; D058127:Transcription Factor 3; D014157:Transcription Factors