First Author | Duan L | Year | 2021 |
Journal | Immunity | Volume | 54 |
Issue | 10 | Pages | 2256-2272.e6 |
PubMed ID | 34555336 | Mgi Jnum | J:321362 |
Mgi Id | MGI:6856544 | Doi | 10.1016/j.immuni.2021.08.028 |
Citation | Duan L, et al. (2021) Follicular dendritic cells restrict interleukin-4 availability in germinal centers and foster memory B cell generation. Immunity 54(10):2256-2272.e6 |
abstractText | 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. |