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J. Exp. Med.,
Volume 188, Number 4, August 17, 1998 699-713
By
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
,
5, and Rag-1, and the ability to induce
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.
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