Function and Regulation of Early B Cell Factor (EBF)

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DESCRIPTION (provided by applicant): Early B cell Factor (EBF) is essential for the development of B lymphocytes from early progenitor cells. EBF regulates the mb-1 gene, which encodes Ig-alpha a protein required for display of immunoglobulin (Ig) on the plasma membrane and transmembrane signaling following stimulation of the B cell receptor (BCR). Cell surface expression of the BCR and the surrogate pro-BCR and pre-BCR at early stages of development is very precisely regulated, and this regulation is critical for proper development and function of B cells. We have observed changes in levels of mb-1 transcripts in cell lines representing different stages of development and in ex vivo B cells following stimulation by polyvalent antigen. As a potential mechanism for setting the level of Ig-alpha in B cells, we recently defined constellations of nuclear factors required for high vs. low level mb-1 transcription at different stages of B cell development. High level transcription requires EBF, the basic-helix-loop-helix (HLH) factor E2A, and the Runt domain protein Runxl (and its coactivator CBFbeta), which assemble higher order complexes on the mb-1 promoter. We propose that the intracellular concentration of Ig-alpha, and thus, expression of the BCR on the surface of B cells, is regulated by EBF and associated proteins. To better understand the molecular biology of EBF, we will determine how it controls B cell development and BCR density, and thus, the response of B cells to antigen.