The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/8/699/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 4, August 17, 1998 699-713


Articles

Induction of Early B Cell Factor (EBF) and Multiple B Lineage Genes by the Basic Helix-Loop-Helix Transcription Factor E12

Barbara L. Kee and Cornelis Murre

From the Department of Biology, University of California San Diego, La Jolla, California 92093

The transcription factors encoded by the E2A and early B cell factor (EBF) genes are required for the proper development of B lymphocytes. However, the absence of B lineage cells in E2A- and EBF-deficient mice has made it difficult to determine the function or relationship between these proteins. We report the identification of a novel model system in which the role of E2A and EBF in the regulation of multiple B lineage traits can be studied. We found that the conversion of 70Z/3 pre-B lymphocytes to cells with a macrophage-like phenotype is associated with the loss of E2A and EBF. Moreover, we show that ectopic expression of the E2A protein E12 in this macrophage line results in the induction of many B lineage genes, including EBF, IL7R{alpha}, {lambda}5, and Rag-1, and the ability to induce {kappa} light chain in response to mitogen. Activation of EBF may be one of the critical functions of E12 in regulating the B lineage phenotype since expression of EBF alone leads to the activation of a subset of E12-inducible traits. Our data demonstrate that, in the context of this macrophage line, E12 induces expression of EBF and together these transcription factors coordinately regulate numerous B lineage–associated genes.

Key Words: B cell development • transcription • lineage determination • gene expression


Address correspondence to Dr. Barbara Kee, Department of Biology, University of California San Diego, 9500 Gilman Dr., MC 0366, La Jolla, CA 92093-0366. Phone: 619-534-8797; Fax: 619-534-7550; E-mail: bkee{at}biomail.ucsd.edu

B.L. Kee was supported by a fellowship from the Medical Research Council of Canada and is a Special Fellow of the Leukemia Society of America. This work was funded by the National Institutes of Health (NIH), the Council for Tobacco Research and the Edward Mallinckrodt Jr. Foundation.

Abbreviations used: bHLH, basic helix-loop-helix; c-fms, macrophage colony-stimulating factor; EBF, early B cell factor; EMSA, electrophoretic mobility shift assay; RT, reverse transcriptase.


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