HUMORAL IMMUNITY. T cell help controls the speed of the cell cycle in germinal center B cells.
HUMORAL IMMUNITY. T cell help controls the speed of the cell cycle in germinal center B cells.
复制标题
DOI：
10.1126/science.aac4919
复制
发表时间：
2015-08-07
期刊：
影响因子：
--
通讯作者：
Nussenzweig MC
中科院分区：
文献类型：
--
作者：
Gitlin AD;Mayer CT;Oliveira TY;Shulman Z;Jones MJ;Koren A;Nussenzweig MC
生发中心（GC）是一个微解剖区室，其中高亲和力抗体产生B细胞被选择性扩增。B细胞在GC的暗区（DZ）中增殖并使其抗体基因突变，然后基于亲和力被亮区（LZ）中的T细胞选择。在这里，我们表明，T细胞的帮助调节细胞周期的相变和GC B细胞的DNA复制的速度。基因组测序和单分子分析表明，T细胞通过调节复制叉的进展，同时保持复制起点激活的相对顺序，帮助缩短S期。因此，高亲和力GC B细胞是通过一种机制选择的，该机制涉及在DZ中延长的停留时间，其中所选细胞经历加速的细胞周期。
The germinal center (GC) is a microanatomical compartment wherein high affinity antibody-producing B cells are selectively expanded. B cells proliferate and mutate their antibody genes in the dark zone (DZ) of the GC, and are then selected by T cells in the light zone (LZ) on the basis of affinity. Here we show that T cell help regulates the speed of cell cycle phase transitions and DNA replication of GC B cells. Genome sequencing and single-molecule analyses revealed that T cell help shortens S phase by regulating replication fork progression while preserving the relative order of replication origin activation. Thus, high affinity GC B cells are selected by a mechanism that involves prolonged dwell time in the DZ where selected cells undergo accelerated cell cycles.