Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel.
J Exp Med. 2019 Nov 4;216(11):2515-2530. doi: 10.1084/jem.20190789. Epub 2019 Sep 6.
Germinal centers (GCs) are sites wherein B cells proliferate and mutate their immunoglobulins in the dark zone (DZ), followed by affinity-based selection in the light zone (LZ). Here, we mapped the location of single B cells in the context of intact lymph nodes (LNs) throughout the GC response, and examined the role of BCR affinity in dictating their position. Imaging of entire GC structures and proximal single cells by light-sheet fluorescence microscopy revealed that individual B cells that previously expressed AID are located within the LN cortex, in an area close to the GC LZ. Using in situ photoactivation, we demonstrated that B cells migrate from the LZ toward the GC outskirts, while DZ B cells are confined to the GC. B cells expressing very-low-affinity BCRs formed GCs but were unable to efficiently disperse within the follicles. Our findings reveal that BCR affinity regulates B cell positioning during the GC response.
生发中心（GCs）是 B 细胞在暗区（DZ）增殖和突变免疫球蛋白的场所，随后在亮区（LZ）进行基于亲和力的选择。在这里，我们在整个 GC 反应过程中绘制了完整淋巴结（LN）中单个 B 细胞的位置，并研究了 BCR 亲和力在决定其位置中的作用。通过光片荧光显微镜对整个 GC 结构和近端单细胞进行成像，结果表明，先前表达 AID 的单个 B 细胞位于 LN 皮质内，靠近 GC LZ。利用原位光激活，我们证明 B 细胞从 LZ 向 GC 外周迁移，而 DZ B 细胞则局限于 GC 内。表达低亲和力 BCR 的 B 细胞形成 GC，但无法在滤泡内有效地扩散。我们的研究结果表明，BCR 亲和力在 GC 反应期间调节 B 细胞的定位。
