Klein Ulf, Casola Stefano, Cattoretti Giorgio, Shen Qiong, Lia Marie, Mo Tongwei, Ludwig Thomas, Rajewsky Klaus, Dalla-Favera Riccardo
Institute for Cancer Genetics, Department of Pathology and Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA.
Nat Immunol. 2006 Jul;7(7):773-82. doi: 10.1038/ni1357. Epub 2006 Jun 11.
B cells producing high-affinity antibodies are destined to differentiate into memory B cells and plasma cells, but the mechanisms leading to those differentiation pathways are mostly unknown. Here we report that the transcription factor IRF4 is required for the generation of plasma cells. Transgenic mice with conditional deletion of Irf4 in germinal center B cells lacked post-germinal center plasma cells and were unable to differentiate memory B cells into plasma cells. Plasma cell differentiation required IRF4 as well as the transcriptional repressor Blimp-1, which both acted 'upstream' of the transcription factor XBP-1. In addition, IRF4-deficient B cells had impaired expression of activation-induced deaminase and lacked class-switch recombination, suggesting an independent function for IRF4 in this process. These results identify IRF4 as a crucial transcriptional 'switch' in the generation of functionally competent plasma cells.
产生高亲和力抗体的B细胞注定会分化为记忆B细胞和浆细胞，但导致这些分化途径的机制大多未知。在此，我们报告转录因子IRF4是浆细胞产生所必需的。在生发中心B细胞中条件性缺失Irf4的转基因小鼠缺乏生发中心后浆细胞，并且无法将记忆B细胞分化为浆细胞。浆细胞分化需要IRF4以及转录抑制因子Blimp-1，二者均作用于转录因子XBP-1的“上游”。此外，缺乏IRF4的B细胞中激活诱导脱氨酶的表达受损，并且缺乏类别转换重组，这表明IRF4在此过程中具有独立功能。这些结果确定IRF4是产生功能健全浆细胞过程中的关键转录“开关”。
