Alexander Lou-Ella M M, Watters January, Reusch Jessica A, Maurin Michelle, Nepon-Sixt Brook S, Vrzalikova Katerina, Alexandrow Mark G, Murray Paul G, Wright Kenneth L
Cancer Biology Ph.D. Program, University of South Florida, Tampa, FL 33612, United States; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Mol Immunol. 2017 Nov;91:8-16. doi: 10.1016/j.molimm.2017.08.016. Epub 2017 Aug 31.
B cell activation is dependent on a large increase in transcriptional output followed by focused expression on secreted immunoglobulin as the cell transitions to an antibody producing plasma cell. The rapid transcriptional induction is facilitated by the release of poised RNA pol II into productive elongation through assembly of the super elongation complex (SEC). We report that a SEC component, the Eleven -nineteen Lysine-rich leukemia (ELL) family member 3 (ELL3) is dynamically up-regulated in mature and activated human B cells followed by suppression as B cells transition to plasma cells in part mediated by the transcription repressor PRDM1. Burkitt's lymphoma and a sub-set of Diffuse Large B cell lymphoma cell lines abundantly express ELL3. Depletion of ELL3 in the germinal center derived lymphomas results in severe disruption of DNA replication and cell division along with increased DNA damage and cell death. This restricted utilization and survival dependence reveal a key step in B cell activation and indicate a potential therapeutic target against B cell lymphoma's with a germinal center origin.
B细胞活化依赖于转录输出的大幅增加，随后随着细胞转变为产生抗体的浆细胞，分泌型免疫球蛋白会集中表达。通过组装超级延伸复合物（SEC），使 poised RNA pol II 释放到有生产性的延伸中，从而促进快速转录诱导。我们报告称，SEC 组件富含 11-19 赖氨酸的白血病（ELL）家族成员 3（ELL3）在成熟和活化的人 B 细胞中动态上调，随后随着 B 细胞向浆细胞转变而受到抑制，部分是由转录抑制因子 PRDM1 介导的。伯基特淋巴瘤和弥漫性大 B 细胞淋巴瘤细胞系的一个亚组大量表达 ELL3。生发中心来源的淋巴瘤中 ELL3 的缺失会导致 DNA 复制和细胞分裂的严重破坏，同时增加 DNA 损伤和细胞死亡。这种有限的利用和生存依赖性揭示了 B 细胞活化中的一个关键步骤，并表明针对生发中心起源的 B 细胞淋巴瘤有潜在的治疗靶点。
