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Remodeling of light and dark zone follicular dendritic cells governs germinal center responses

Journal Paper/Review - May 18, 2020

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Citation
Pikor N, Onder L, Linterman M, Nagasawa T, Nombela-Arrieta C, Cheng H, Novkovic M, Perez Shibayama C, Gil Cruz C, Lütge M, Mörbe U, 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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Journal Paper/Review (English)
Journal
Nat Immunol 2020; 21
Publication Date
May 18, 2020
Issn Print
Issn Electronic
1529-2916
Pages
649-659
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Brief description/objective

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.