Identification of a new subset of lymph node stromal cells involved in regulating plasma cell homeostasis

Antibody-secreting plasma cells (PC) arise rapidly during adaptive immunity to control infections. The early PC are retained within the reactive lymphoid organ where their localization and homeostasis relies on extrinsic factors, presumably produced by local niche cells. While myeloid cells have been proposed to form those niches, the contribution by co-localizing stromal cells has remained unclear. Here, we characterized a subset of fibroblastic reticular cells (FRC) that forms a dense meshwork throughout medullary cords of lymph nodes (LN) where PC reside. This medullary FRC type is shown to be anatomically, phenotypically and functionally distinct from T zone FRC, both in mice and humans. By using static and dynamic imaging approaches, we provide evidence that medullary FRC are the main cell type in contact with PC guiding them in their migration. Medullary FRC also represent a major local source of the PC survival factors IL-6, BAFF and CXCL12, besides producing also APRIL. In vitro, medullary FRC alone or in combination with macrophages promote PC survival while other LN cell types do not have this property. Thus, we propose that this new FRC subset, together with medullary macrophages, forms PC survival niches within the LN medulla, and thereby helps promoting the rapid development of humoral immunity which is critical in limiting early pathogen spread.