Kusam Saritha, Dent Alexander
Department of Microbiology and Immunology and The Walther Oncology Center, Indiana University School of Medicine, 950 W. Walnut St. R2 302, Indianapolis, IN 46202, USA.
Immunol Res. 2007;37(3):177-86. doi: 10.1007/BF02697368.
The BCL-6 transcriptional repressor protein is a critical regulator of normal B cell differentiation and BCL-6 has recently been shown to act as an oncogene in several mouse model systems. The molecular pathways by which BCL-6 regulates B cell differentiation and also promotes the transformation of primary B cells are undoubtedly related; however, these pathways are poorly understood. The commonly accepted model for BCL-6 function in B cells is that BCL-6 inhibits the terminal differentiation of activated B cells into plasma cells and that deregulation of BCL-6 expression leads to an inhibition of terminal differentiation and continued proliferation. BCL-6 induces a germinal-center phenotype in primary B cells by unknown mechanisms, and can reverse the terminal differentiation of plasma cell tumor lines. BCL-6 can promote the immortalization of primary B cells and can augment telomerase activity. The role of the vast majority of BCL-6 target genes and interacting proteins in normal B cell differentiation and B cell transformation is essentially unresolved and is an important area for future investigation.
BCL-6转录抑制蛋白是正常B细胞分化的关键调节因子，最近在多个小鼠模型系统中已证明BCL-6可作为一种癌基因。BCL-6调节B细胞分化并促进原代B细胞转化的分子途径无疑是相关的；然而，这些途径目前还知之甚少。关于BCL-6在B细胞中功能的普遍接受的模型是，BCL-6抑制活化的B细胞向浆细胞的终末分化，并且BCL-6表达失调会导致终末分化受到抑制并持续增殖。BCL-6通过未知机制在原代B细胞中诱导生发中心表型，并可逆转浆细胞瘤系的终末分化。BCL-6可促进原代B细胞的永生化，并可增强端粒酶活性。绝大多数BCL-6靶基因和相互作用蛋白在正常B细胞分化和B细胞转化中的作用基本上尚未明确，是未来研究的一个重要领域。
