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

Natalia Pikor, Urs Mörbe, Mechthild Lütge, Cristina Gil Cruz, Christian Perez Shibayama, Mario Novkovic, Hung-Wei Cheng, César Nombela-Arrieta, Takashi Nagasawa, Michelle A Linterman, Lucas Onder & Burkhard Ludewig

abstract 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.
   
citation 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.
   
type journal paper/review (English)
date of publishing 18-05-2020
journal title Nat Immunol (21/6)
ISSN electronic 1529-2916
pages 649-659
PubMed 32424359
DOI 10.1038/s41590-020-0672-y