Organizer-Like Reticular Stromal Cell Layer Common to Adult Secondary Lymphoid Organs

TLDR

Mesenchymal stromal cells are essential for secondary lymphoid organ structure and function, yet the link between embryonic lymphoid tissue organizers and adult stromal lineages, as well as the exact number of stromal cell types in mature SLOs, remains poorly defined. The authors derived a VCAM‑1⁺ICAM‑1⁺MAdCAM‑1⁺ reticular cell line from mouse lymph nodes that, upon LTβR stimulation, secretes CXCL13 and supports primary B‑cell adhesion and migration in vitro. They identified marginal reticular cells (MRCs), a VCAM‑1⁺ICAM‑1⁺MAdCAM‑1⁺ population resembling lymphoid tissue organizers, present in the outer follicular region of lymph nodes and other SLOs even in Rag2−/− mice, absent from ectopic lymphoid tissues, thereby defining a developmentally determined stromal component that informs the overall composition and architecture of secondary lymphoid organs.

Abstract

Abstract Mesenchymal stromal cells are crucial components of secondary lymphoid organs (SLOs). Organogenesis of SLOs involves specialized stromal cells, designated lymphoid tissue organizer (LTo) in the embryonic anlagen; in the adult, several distinct stromal lineages construct elaborate tissue architecture and regulate lymphocyte compartmentalization. The relationship between the LTo and adult stromal cells, however, remains unclear, as does the precise number of stromal cell types that constitute mature SLOs are unclear. From mouse lymph nodes, we established a VCAM-1+ICAM-1+MAdCAM-1+ reticular cell line that can produce CXCL13 upon LTβR stimulation and support primary B cell adhesion and migration in vitro. A similar stromal population sharing many characteristics with the LTo, designated marginal reticular cells (MRCs), was found in the outer follicular region immediately underneath the subcapsular sinus of lymph nodes. Moreover, MRCs were commonly observed at particular sites in various SLOs even in Rag2−/− mice, but were not found in ectopic lymphoid tissues, suggesting that MRCs are a developmentally determined element. These findings lead to a comprehensive view of the stromal composition and architecture of SLOs.