Molecular Immunology Division, 2 Bioinformatics Division, 3 Immunology Division, The Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia.
J Exp Med. 2014 May 5;211(5):827-40. doi: 10.1084/jem.20131831. Epub 2014 Apr 7.
The transcriptional network regulating antibody-secreting cell (ASC) differentiation has been extensively studied, but our current understanding is limited. The mechanisms of action of known "master" regulators are still unclear, while the participation of new factors is being revealed. Here, we identify Zbtb20, a Bcl6 homologue, as a novel regulator of late B cell development. Within the B cell lineage, Zbtb20 is specifically expressed in B1 and germinal center B cells and peaks in long-lived bone marrow (BM) ASCs. Unlike Bcl6, an inhibitor of ASC differentiation, ectopic Zbtb20 expression in primary B cells facilitates terminal B cell differentiation to ASCs. In plasma cell lines, Zbtb20 induces cell survival and blocks cell cycle progression. Immunized Zbtb20-deficient mice exhibit curtailed humoral responses and accelerated loss of antigen-specific plasma cells, specifically from the BM pool. Strikingly, Zbtb20 induction does not require Blimp1 but depends directly on Irf4, acting at a newly identified Zbtb20 promoter in ASCs. These results identify Zbtb20 as an important player in late B cell differentiation and provide new insights into this complex process.
调控抗体分泌细胞（ASC）分化的转录网络已经得到了广泛研究，但我们目前的理解仍然有限。已知“主”调控因子的作用机制尚不清楚，而新的因素的参与正在被揭示。在这里，我们鉴定出 Zbtb20 是 B 细胞发育后期的一个新的调控因子，是 Bcl6 的同源物。在 B 细胞谱系中，Zbtb20 特异性地在 B1 和生发中心 B 细胞中表达，并在长寿命的骨髓（BM）ASC 中达到峰值。与抑制 ASC 分化的 Bcl6 不同，原代 B 细胞中异位表达 Zbtb20 有助于 B 细胞终末分化为 ASC。在浆细胞瘤系中，Zbtb20 诱导细胞存活并阻止细胞周期进程。免疫的 Zbtb20 缺陷小鼠表现出减弱的体液反应和加速丧失抗原特异性浆细胞，特别是从 BM 池。引人注目的是，Zbtb20 的诱导不需要 Blimp1，而是直接依赖于 Irf4，在 ASC 中的一个新鉴定的 Zbtb20 启动子上发挥作用。这些结果确定 Zbtb20 是晚期 B 细胞分化的重要参与者，并为这一复杂过程提供了新的见解。
