Department of Pathology and Cell Biology, Institute for Cancer Genetics, the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
Immunol Rev. 2012 May;247(1):172-83. doi: 10.1111/j.1600-065X.2012.01112.x.
BCL6 is a transcriptional repressor required in mature B cells during the germinal center (GC) reaction. Multiple mechanisms act coordinately to timely modulate BCL6 expression at transcriptional and post-transcriptional levels. BCL6 prevents premature activation and differentiation of GC B cells and provides an environment tolerant of the DNA breaks associated with immunoglobulin gene remodeling mechanisms involved in the production of high-affinity antibodies of different isotypes. The critical functions exerted by BCL6 during normal B-cell development can be hijacked by the malignant transformation process. Indeed, BCL6 is targeted by genetic aberrations and acts as an oncogene in GC-derived lymphomas. The aberrations affecting BCL6 interfere with the multiple levels of regulation that grant a fine tuning of BCL6 expression and activity in physiologic conditions. This review summarizes the current knowledge on BCL6 function and its role in lymphomagenesis.
BCL6 是生发中心（GC）反应中成熟 B 细胞所必需的转录抑制因子。多种机制协同作用，在转录和转录后水平上及时调节 BCL6 的表达。BCL6 可防止 GC B 细胞过早激活和分化，并为与免疫球蛋白基因重排机制相关的 DNA 断裂提供耐受环境，该机制参与产生不同同种型的高亲和力抗体。BCL6 在正常 B 细胞发育过程中发挥的关键功能可被恶性转化过程劫持。事实上，BCL6 是遗传异常的靶点，并且在 GC 衍生的淋巴瘤中作为癌基因发挥作用。影响 BCL6 的异常干扰了赋予生理条件下 BCL6 表达和活性精细调节的多个调节水平。这篇综述总结了 BCL6 功能及其在淋巴瘤发生中的作用的最新知识。
