@article{f616281a22064f928382ee621bce2afd,
title = "Follicular dendritic cells restrict interleukin-4 availability in germinal centers and foster memory B cell generation",
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.",
keywords = "IL-4, affinity maturation, follicular dendritic cells, germinal center, memory B cells, scRNA-seq, scVDJ-seq",
author = "Lihui Duan and Dan Liu and Hsin Chen and Mintz, {Michelle A.} and Chou, {Marissa Y.} and Kotov, {Dmitri I.} and Ying Xu and Jinping An and Laidlaw, {Brian J.} and Cyster, {Jason G.}",
note = "Funding Information: We thank Chris Allen, Mark Ansel, Marlys Fassett, Rich Locksley, Burkhard Ludewig, and Takaharu Okada for the mice. This work was supported by grants from the NIH ( R01AI045073 ). D.L. and H.C. were supported by the Irvington Cancer Research Institute . J.G.C. is an investigator of the Howard Hughes Medical Institute. Funding Information: We thank Chris Allen, Mark Ansel, Marlys Fassett, Rich Locksley, Burkhard Ludewig, and Takaharu Okada for the mice. This work was supported by grants from the NIH (R01AI045073). D.L. and H.C. were supported by the Irvington Cancer Research Institute. J.G.C. is an investigator of the Howard Hughes Medical Institute. L.D. D.L. and J.G.C. designed the study; L.D. and D.L. performed the experiments; H.C. and M.A.M. generated cells for scRNA-seq and scVDJ-seq in Figures 1, 2, and 3; L.D. performed the scRNA-seq and scVDJ-seq analyses; H.C. and M.Y.C. characterized the AS20-OVA reagent; D.I.K. generated the pMCP-BFP vector; Y.X. generated AS20-OVA; J.A. screened the mice; B.J.L. provided input on the memory B cell characterization; L.D. D.L. and J.G.C. analyzed the data and wrote the manuscript. J.G.C. is an Scientific Advisory Board member of Be Biopharma and MiroBio. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = oct,
day = "12",
doi = "10.1016/j.immuni.2021.08.028",
language = "English",
volume = "54",
pages = "2256--2272.e6",
journal = "Immunity",
issn = "1074-7613",
number = "10",
}