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

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.
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