Carotta Sebastian, Willis Simon N, Hasbold Jhagvaral, Inouye Michael, Pang Swee Heng Milon, Emslie Dianne, Light Amanda, Chopin Michael, Shi Wei, Wang Hongsheng, Morse Herbert C, Tarlinton David M, Corcoran Lynn M, Hodgkin Philip D, Nutt Stephen L
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
J Exp Med. 2014 Oct 20;211(11):2169-81. doi: 10.1084/jem.20140425. Epub 2014 Oct 6.
Activated B cells undergo immunoglobulin class-switch recombination (CSR) and differentiate into antibody-secreting plasma cells. The distinct transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors: those that maintain the B cell program, including BCL6 and PAX5, and plasma cell-promoting factors, such as IRF4 and BLIMP-1. We show that the complex of IRF8 and PU.1 controls the propensity of B cells to undergo CSR and plasma cell differentiation by concurrently promoting the expression of BCL6 and PAX5 and repressing AID and BLIMP-1. As the PU.1-IRF8 complex functions in a reciprocal manner to IRF4, we propose that concentration-dependent competition between these factors controls B cell terminal differentiation.
活化的B细胞经历免疫球蛋白类别转换重组（CSR）并分化为分泌抗体的浆细胞。B细胞和浆细胞独特的转录组由两组转录因子的拮抗作用维持：一组维持B细胞程序，包括BCL6和PAX5；另一组促进浆细胞生成，如IRF4和BLIMP-1。我们发现，IRF8和PU.1复合物通过同时促进BCL6和PAX5的表达以及抑制AID和BLIMP-1，控制B细胞进行CSR和浆细胞分化的倾向。由于PU.1-IRF8复合物与IRF4以相互作用的方式发挥作用，我们提出这些因子之间的浓度依赖性竞争控制B细胞的终末分化。
