期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 29, 页码 E6826-E6835出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1712628115
关键词
FRC subsets; lymph node medulla; extrafollicular B cell differentiation; plasma cell survival; humoral response
资金
- Swiss National Science Foundation [31003-146944/1]
- Taiwan National Science Council [NSC 100-2917-I-564-005]
- French Ligue Nationale Contre le Cancer [EL2014.LNCC/ED]
- Agence Nationale de la Recherche [CHEMIMMUN ANR-13-BSV3-0010]
- Cancer Research for Personalized Medicine
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.
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