Abstract:
:Antibody-secreting plasma cells (PCs) arise rapidly during adaptive immunity to control infections. The early PCs are retained within the reactive lymphoid organ where their localization and homeostasis rely on extrinsic factors, presumably produced by local niche cells. While myeloid cells have been proposed to form those niches, the contribution by colocalizing stromal cells has remained unclear. Here, we characterized a subset of fibroblastic reticular cells (FRCs) that forms a dense meshwork throughout medullary cords of lymph nodes (LNs) where PCs reside. This medullary FRC type is shown to be anatomically, phenotypically, and functionally distinct from T zone FRCs, both in mice and humans. By using static and dynamic imaging approaches, we provide evidence that medullary FRCs are the main cell type in contact with PCs guiding them in their migration. Medullary FRCs also represent a major local source of the PC survival factors IL-6, BAFF, and CXCL12, besides also producing APRIL. In vitro, medullary FRCs alone or in combination with macrophages promote PC survival while other LN cell types do not have this property. Thus, we propose that this FRC subset, together with medullary macrophages, forms PC survival niches within the LN medulla, and thereby helps in promoting the rapid development of humoral immunity, which is critical in limiting early pathogen spread.
journal_name
Proc Natl Acad Sci U S Aauthors
Huang HY,Rivas-Caicedo A,Renevey F,Cannelle H,Peranzoni E,Scarpellino L,Hardie DL,Pommier A,Schaeuble K,Favre S,Vogt TK,Arenzana-Seisdedos F,Schneider P,Buckley CD,Donnadieu E,Luther SAdoi
10.1073/pnas.1712628115subject
Has Abstractpub_date
2018-07-17 00:00:00pages
E6826-E6835issue
29eissn
0027-8424issn
1091-6490pii
1712628115journal_volume
115pub_type
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