美国加州大学旧金山分校Jason G. Cyster研究组发现，滤泡树突状细胞限制白细胞介素-4在生发中心的可用性并促进记忆B细胞的生成。2021年9月22日，《免疫》杂志在线发表了这项成果。

研究人员揭示了白细胞介素（IL）-4对生发中心（GC）内B细胞命运决定的贡献。单细胞RNA测序确定了亮区GC B细胞的一个亚群，表达高IL-4受体-a（IL4Ra）和CD23，并缺乏Myc相关的特征。这些细胞可以分化为前记忆细胞。B细胞特异性缺失IL4Ra或STAT6有利于前记忆细胞的发育，而在野生型背景下提供外源性IL-4可减少前记忆细胞的频率。IL-4在抗原特异性相互作用中起作用，但也影响了旁观者的细胞。

滤泡树突状细胞（FDC）中IL4Ra的缺失增加了GC中IL-4的可用性，损害了亲和力成熟的B细胞的选择，并减少了记忆细胞的生成。研究人员提出，GC FDC建立了一个限制旁观者IL-4活性的微环境，使IL-4作用于正在进行选择的B细胞并增强记忆细胞的分化。

据介绍，GC内的B细胞进入抗体亲和力成熟的周期或作为记忆细胞或浆细胞退出GC。

附：英文原文

Title: Follicular dendritic cells restrict interleukin-4 availability in germinal centers and foster memory B cell generation

Author: Lihui Duan, Dan Liu, Hsin Chen, Michelle A. Mintz, Marissa Y. Chou, Dmitri I. Kotov, Ying Xu, Jinping An, Brian J. Laidlaw, Jason G. Cyster

Issue&Volume: 2021-09-22

Abstract: B cells within germinal centers (GCs) enter cycles of antibody affinity maturationor exit the GC as memory cells or plasma cells. Here, we examined the contributionof interleukin (IL)-4 on B cell fate decisions in the GC. Single-cell RNA-sequencingidentified 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 intopre-memory cells. B cell-specific deletion of IL4Ra or STAT6 favored the pre-memorycell trajectory, and provision of exogenous IL-4 in a wild-type context reduced pre-memorycell frequencies. IL-4 acted during antigen-specific interactions but also influencedbystander cells. Deletion of IL4Ra from follicular dendritic cells (FDCs) increasedthe 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 thatlimits bystander IL-4 activity, focusing IL-4 action on B cells undergoing selectionand enhancing memory cell differentiation.

DOI: 10.1016/j.immuni.2021.08.028

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00362-9