Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.
Nature. 2014 May 29;509(7502):637-40. doi: 10.1038/nature13300. Epub 2014 May 4.
During immune responses, B lymphocytes clonally expand and undergo secondary diversification of their immunoglobulin genes in germinal centres (GCs). High-affinity B cells are expanded through iterative interzonal cycles of division and hypermutation in the GC dark zone followed by migration to the GC light zone, where they are selected on the basis of affinity to return to the dark zone. Here we combine a transgenic strategy to measure cell division and a photoactivatable fluorescent reporter to examine whether the extent of clonal expansion and hypermutation are regulated during interzonal GC cycles. We find that both cell division and hypermutation are directly proportional to the amount of antigen captured and presented by GC B cells to follicular helper T cells in the light zone. Our data explain how GC B cells with the highest affinity for antigen are selectively expanded and diversified.
在免疫反应过程中，B 淋巴细胞通过克隆扩增，并在生发中心（GC）中进行免疫球蛋白基因的二次多样化。高亲和力的 B 细胞通过在 GC 暗区的分裂和超突变的迭代区室间循环扩增，然后迁移到 GC 亮区，在那里它们根据亲和力被选择回到暗区。在这里，我们结合了一种转基因策略来测量细胞分裂，并使用光活化荧光报告来检查在区室间 GC 循环中克隆扩增和超突变的程度是否受到调节。我们发现，细胞分裂和超突变都与 GC B 细胞在亮区中捕获和呈递抗原的量成正比。我们的数据解释了 GC B 细胞如何选择性地扩增和多样化对抗原具有最高亲和力的细胞。
