Remodeling of light and dark zone follicular dendritic cells governs germinal center responses
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abstract
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Efficient generation of germinal center (GC) responses requires
directed movement of B cells between distinct microenvironments
underpinned by specialized B cell-interacting reticular cells
(BRCs). How BRCs are reprogrammed to cater to the developing GC
remains unclear, and studying this process is largely hindered by
incomplete resolution of the cellular composition of the B cell
follicle. Here we used genetic targeting of Cxcl13-expressing cells
to define the molecular identity of the BRC landscape. Single-cell
transcriptomic analysis revealed that BRC subset specification was
predetermined in the primary B cell follicle. Further topological
remodeling of light and dark zone follicular dendritic cells
required CXCL12-dependent crosstalk with B cells and dictated GC
output by retaining B cells in the follicle and steering their
interaction with follicular helper T cells. Together, our results
reveal that poised BRC-defined microenvironments establish a
feed-forward system that determines the efficacy of the GC reaction.
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citation
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Pikor N, Mörbe U, Lütge M, Gil Cruz C, Perez Shibayama C, Novkovic
M, Cheng H W, Nombela-Arrieta C, Nagasawa T, Linterman M A, Onder L,
Ludewig B. Remodeling of light and dark zone follicular dendritic
cells governs germinal center responses. Nat Immunol 2020;
21:649-659.
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type
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journal paper/review (English)
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date of publishing
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18-05-2020
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journal title
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Nat Immunol (21/6)
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ISSN electronic
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1529-2916
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pages
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649-659
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PubMed
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32424359
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DOI
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10.1038/s41590-020-0672-y
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