FIGURE 8.

Model for the role of C/EBPα in early B lymphopoiesis. (A) Multipotent Cebpa^int Flt3⁺ CLP predominantly generate Cebpa^int preproB, which give rise to myeloid cells or to Cebpa^lo preproB, the latter progressing to the Cebpa^neg proB stage. Efficient Flt3⁺ CLP to preproB and preproB to proB progression requires C/EBPα (α). PreproB express both myeloid and lymphoid TFs, as listed, whereas proB cells down-modulate myeloid TFs and express increased levels of several lymphoid TFs (denoted by larger font) and Pax5. (B) Gene regulatory network linking TFs that control B lineage commitment and progression. Ikaros induces E2A, EBF1, and Foxo1, which then induce each other and Pax5. E2A, EBF1, Foxo1, and Pax5 cooperatively activate genes such as Mb1 and CD19 to specify the proB stage. Bach2 is induced by B lineage TFs and represses Cebpa (and Cebpb) to suppress myelopoiesis, while inducing Foxo1 to further favor B lymphopoiesis. C/EBPα may contribute to B lymphopoiesis by inducing PU.1, which cooperates with IRF4/IRF8 to induce Pax5, and by directly stimulating Bach2 gene expression.