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

被引:206
作者
Cremasco, Viviana [1 ]
Woodruff, Matthew C. [2 ,3 ]
Onder, Lucas [4 ]
Cupovic, Jovana [4 ]
Nieves-Bonilla, Janice M. [1 ]
Schildberg, Frank A. [1 ]
Chang, Jonathan [1 ,3 ]
Cremasco, Floriana [1 ,5 ]
Harvey, Christopher J. [1 ]
Wucherpfennig, Kai [1 ]
Ludewig, Burkhard [4 ]
Carroll, Michael C. [2 ,6 ]
Turley, Shannon J. [1 ,7 ]
机构
[1] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA
[2] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Div Med Sci, Boston, MA 02115 USA
[4] Kantonal Hosp St Gallen, Inst Immunol, St Gallen, Switzerland
[5] Univ Milan, Dept Pharmacol, Milan, Italy
[6] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
SECONDARY LYMPHOID ORGANS; BETA-DEFICIENT MICE; DENDRITIC CELLS; HUMORAL IMMUNITY; STROMAL CELLS; NODES; ANTIGEN; ORGANOGENESIS; ACTIVATION; MATURATION;
D O I
10.1038/ni.2965
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:973 / U222
页数:11
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