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

Cremasco, Viviana; Woodruff, Matthew C.; Onder, Lucas; Cupovic, Jovana; Nieves-Bonilla, Janice M.; Schildberg, Frank A.; Chang, Jonathan; Cremasco, Floriana; Harvey, Christopher J.; Wucherpfennig, Kai; Ludewig, Burkhard; Carroll, Michael C.; Turley, Shannon J.

Fibroblastic reticular cells (FRCs) are known to inhabit T cell-rich areas of lymphoid organs where they function to coordinate T cell and dendritic cell interactions. However, in vivo manipulation of FRCs has been limited by a dearth of genetic tools targeting this lineage. Here, using a mouse model to conditionally ablate FRCs, we demonstrate their indispensable role in anti-viral T cell responses. Unexpectedly, FRC loss 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 illuminates a subset of FRCs that controls B cell homeostasis and follicle identity.