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

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2256-2272.e6
JournalImmunity
Volume54
Issue number10
DOIs
StatePublished - Oct 12 2021

Keywords

  • IL-4
  • affinity maturation
  • follicular dendritic cells
  • germinal center
  • memory B cells
  • scRNA-seq
  • scVDJ-seq

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