Abstract
Stromal cells have for a long time been viewed as structural cells that support distinct compartments within lymphoid tissues and little more. Instead, an active cross-talk between endothelial and fibroblastic stromal cells drives the maturation of lymphoid niches, a relationship that is recapitulated during lymph node organogenesis, steady-state conditions, and following inflammation. In this review, we go over recent advances in genetic models and high-resolution transcriptomic analyses that have propelled the finer resolution of the stromal cell infrastructure of lymph nodes, revealing that the distinct subsets are strategically positioned to deliver a catered mixture of niche factors to interacting immune cell populations. Moreover, we discuss how changes in the activation state of poised stromal cell–underpinned niches rather than on-demand differentiation of new stromal cell subsets govern the efficient interaction of Ag, APC, and cognate B and T lymphocytes during adaptive immune responses.
Footnotes
This work was supported by the Swiss National Science Foundation Grants 166500 and 159188 (to B.L.) and 180011 (to N.B.P.). The funder had no role in design, decision to publish, or preparation of the manuscript.
Abbreviations used in this article:
- BEC
- blood endothelial cell
- BRC
- B cell–interacting reticular cell
- cLEC
- ceiling LEC
- DC
- dendritic cell
- DZ
- dark zone
- EC
- endothelial cell
- FDC
- follicular DC
- fLEC
- floor-LEC
- FRC
- fibroblastic reticular cell
- GC
- germinal center
- HEC
- high EC
- HEV
- high endothelial venule
- LEC
- lymphatic endothelial cell
- LN
- lymph node
- LNSC
- LN stromal cell
- LTi
- lymphoid tissue inducer
- LTo
- lymphoid tissue organizer
- LTβR
- lymphotoxin-β receptor
- LZ
- light zone
- MedRC
- medullary reticular cell
- PNAd
- peripheral node addressin
- scRNA-seq
- single-cell RNA–sequencing
- SCS
- subcapsular sinus
- TBRC
- T-B border reticular cell
- TRC
- T cell zone reticular cell.
- Received August 3, 2020.
- Accepted October 16, 2020.
- Copyright © 2021 by The American Association of Immunologists, Inc.
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