The Journal of Experimental Medicine
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Published 21 June 2004. doi:10.1084/jem.20032202
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 12, 1689-1700
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Early B Cell Factor Promotes B Lymphopoiesis with Reduced Interleukin 7 Responsiveness in the Absence of E2A

Christopher S. Seet1, Rachel L. Brumbaugh1, and Barbara L. Kee1,2

1 Department of Pathology and 2 Committees on Immunology, Cancer Biology, and Development, University of Chicago, Chicago, IL 60637

Address correspondence to Barbara L. Kee, Department of Pathology, University of Chicago, 5841 S. Maryland Avenue, MC 1089, Chicago, IL 60637. Phone: (773) 702-4349; Fax: (773) 834-5251; email: bkee{at}bsd.uchicago.edu

The basic helix-loop-helix transcription factors encoded by the E2A gene function at the apex of a transcriptional hierarchy involving E2A, early B cell factor (EBF), and Pax5, which is essential for B lymphopoiesis. In committed B lineage progenitors, E2A proteins have also been shown to regulate many lineage-associated genes. Herein, we demonstrate that the block in B lymphopoiesis imposed by the absence of E2A can be overcome by expression of EBF, but not Pax5, indicating that EBF is the essential target of E2A required for development of B lineage progenitors. Our data demonstrate that EBF, in synergy with low levels of alternative E2A-related proteins (E proteins), is sufficient to promote expression of most B lineage genes. Remarkably, however, we find that E2A proteins are required for interleukin 7–dependent proliferation due, in part, to a role for E2A in optimal expression of N-myc. Therefore, high levels of E protein activity are essential for the activation of EBF and N-myc, whereas lower levels of E protein activity, in synergy with other B lineage transcription factors, are sufficient for expression of most B lineage genes.

Key Words: lymphopoiesis • transcription factor • E2A • EBF

Abbreviations used in this paper: bHLH, basic helix-loop-helix; BLP, B lymphocyte progenitor; BrdU, bromodeoxyuridine; EBF, early B cell factor; EMSA, electromobility shift analysis; FL, fetal liver; GFP, green fluorescent protein; KL, c-kit ligand; PI, propidium iodide.


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