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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.