Roles of BCL6 in normal and transformed germinal center B cells

被引:329
作者
Basso, Katia [1 ]
Dalla-Favera, Riccardo [1 ,2 ,3 ]
机构
[1] Columbia Univ, Dept Pathol & Cell Biol, Inst Canc Genet, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA
[2] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA
[3] Columbia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA
关键词
BCL6; germinal center; non-Hodgkin B-cell lymphoma; B-cell differentiation; DNA damage response; TP53; RUBINSTEIN-TAYBI SYNDROME; PROLYL ISOMERASE PIN1; NON-HODGKINS-LYMPHOMA; FINGER ENCODING GENE; AFFECTING BAND 3Q27; TRANSCRIPTION FACTOR; IN-VIVO; NEGATIVE AUTOREGULATION; SOMATIC HYPERMUTATION; PLASMA-CELLS;
D O I
10.1111/j.1600-065X.2012.01112.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:172 / 183
页数:12
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