Function and Regulation of Early B Cell Factor (EBF)

描述（由申请方提供）：早期B细胞因子（EBF）对于从早期祖细胞发育B淋巴细胞至关重要。EBF调节mb-1基因，其编码Ig-α，Ig-α是在质膜上展示免疫球蛋白（IG）和刺激B细胞受体（BCR）后跨膜信号传导所需的蛋白质。在发育的早期阶段，BCR和替代物pro-BCR和pre-BCR的细胞表面表达受到非常精确的调节，并且这种调节对于B细胞的正常发育和功能至关重要。我们已经观察到在代表不同发育阶段的细胞系中和在多价抗原刺激后的离体B细胞中mb-1转录物水平的变化。作为在B细胞中设定Ig-α水平的潜在机制，我们最近定义了在B细胞发育的不同阶段高水平与低水平mb-1转录所需的核因子的星座。高水平转录需要EBF、碱性-螺旋-环-螺旋（HLH）因子E2 A和Runt结构域蛋白Runxl（及其共激活因子CBFbeta），它们在mb-1启动子上组装更高级的复合物。我们认为细胞内Ig-α的浓度以及B细胞表面BCR的表达受EBF和相关蛋白的调节。为了更好地了解EBF的分子生物学，我们将确定它如何控制B细胞发育和BCR密度，从而控制B细胞对抗原的反应。

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.