当前位置: X-MOL 学术Immunity › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Follicular dendritic cells restrict interleukin-4 availability in germinal centers and foster memory B cell generation
Immunity ( IF 32.4 ) Pub Date : 2021-09-22 , DOI: 10.1016/j.immuni.2021.08.028
Lihui Duan 1 , Dan Liu 1 , Hsin Chen 1 , Michelle A Mintz 1 , Marissa Y Chou 1 , Dmitri I Kotov 2 , Ying Xu 1 , Jinping An 1 , Brian J Laidlaw 1 , Jason G Cyster 1
Affiliation  

B cells within germinal centers (GCs) enter cycles of antibody affinity maturation or exit the GC as memory cells or plasma cells. Here, we examined the contribution of interleukin (IL)-4 on B cell fate decisions in the GC. Single-cell RNA-sequencing identified a subset of light zone GC B cells expressing high IL-4 receptor-a (IL4Ra) and CD23 and lacking a Myc-associated signature. These cells could differentiate into pre-memory cells. B cell-specific deletion of IL4Ra or STAT6 favored the pre-memory cell trajectory, and provision of exogenous IL-4 in a wild-type context reduced pre-memory cell frequencies. IL-4 acted during antigen-specific interactions but also influenced bystander cells. Deletion of IL4Ra from follicular dendritic cells (FDCs) increased the availability of IL-4 in the GC, impaired the selection of affinity-matured B cells, and reduced memory cell generation. We propose that GC FDCs establish a niche that limits bystander IL-4 activity, focusing IL-4 action on B cells undergoing selection and enhancing memory cell differentiation.



中文翻译:

滤泡树突状细胞限制生发中心的白细胞介素 4 可用性并促进记忆 B 细胞的产生

生发中心 (GC) 内的 B 细胞进入抗体亲和力成熟周期或作为记忆细胞或浆细胞退出 GC。在这里,我们检查了白细胞介素 (IL)-4 对 GC 中 B 细胞命运决定的贡献。单细胞 RNA 测序确定了轻区 GC B 细胞的一个子集,它们表达高 IL-4 受体-a (IL4Ra) 和 CD23,并且缺乏 Myc 相关的特征。这些细胞可以分化成前记忆细胞。IL4Ra 或 STAT6 的 B 细胞特异性缺失有利于前记忆细胞轨迹,在野生型环境中提供外源性 IL-4 会降低前记忆细胞频率。IL-4 在抗原特异性相互作用期间起作用,但也影响旁观者细胞。从滤泡树突细胞 (FDC) 中删除 IL4Ra 增加了 GC 中 IL-4 的可用性,削弱了亲和力成熟 B 细胞的选择,并减少存储单元的生成。我们建议 GC FDC 建立一个限制旁观者 IL-4 活性的生态位,将 IL-4 作用集中在正在选择的 B 细胞上并增强记忆细胞分化。

更新日期:2021-10-12
down
wechat
bug