[HTML][HTML] B cell homeostasis and follicle confines are governed by fibroblastic reticular cells

V Cremasco, MC Woodruff, L Onder, J Cupovic… - Nature …, 2014 - nature.com
V Cremasco, MC Woodruff, L Onder, J Cupovic, JM Nieves-Bonilla, FA Schildberg, J Chang…
Nature immunology, 2014nature.com
Fibroblastic reticular cells (FRCs) are known to inhabit T cell–rich areas of lymphoid organs,
where they function to facilitate interactions between T cells and dendritic cells. However, in
vivo manipulation of FRCs has been limited by a dearth of genetic tools that target this
lineage. Here, using a mouse model to conditionally ablate FRCs, we demonstrated their
indispensable role in antiviral T cell responses. Unexpectedly, loss of FRCs also attenuated
humoral immunity due to impaired B cell viability and follicular organization. Follicle-resident …
Abstract
Fibroblastic reticular cells (FRCs) are known to inhabit T cell–rich areas of lymphoid organs, where they function to facilitate interactions between T cells and dendritic cells. However, in vivo manipulation of FRCs has been limited by a dearth of genetic tools that target this lineage. Here, using a mouse model to conditionally ablate FRCs, we demonstrated their indispensable role in antiviral T cell responses. Unexpectedly, loss of FRCs also attenuated humoral immunity due to impaired B cell viability and follicular organization. Follicle-resident FRCs established a favorable niche for B lymphocytes via production of the cytokine BAFF. Thus, our study indicates that adaptive immunity requires an intact FRC network and identifies a subset of FRCs that control B cell homeostasis and follicle identity.
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