Open AccessRemodeling of light and dark zone follicular dendritic cells governs germinal center responses
Author(s) -
Natalia Pikor,
Urs Mörbe,
Mechthild Lütge,
Cristina GilCruz,
Christian Pérez-Shibayama,
Mario Novković,
HungWei Cheng,
César NombelaArrieta,
Takashi Nagasawa,
Michelle Linterman,
Lucas Onder,
Burkhard Ludewig
Publication year - 2020
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-020-0672-y
Subject(s) - germinal center , follicular dendritic cells , microbiology and biotechnology , reticular cell , biology , b cell , immune system , chemistry , antigen presenting cell , t cell , immunology , antibody , spleen
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.