Distinct SLOs share key BRC subsets such as follicular dendritic cells (FDCs), while subsets supporting memory B cells (MBCs) in the antigen-sampling zone 16 or plasma cells in the medulla 17 are not ubiquitous across SLOs. SLOs consist of lymph nodes (LNs), Peyer’s patches and splenic white pulp (WP), which differ in their anatomy, developmental origin and surveyed bodily fluids 13, 14, 15. As such, little is known about the functional overlap between BRC subsets or the signals sustaining BRC subset identity. In contrast to the elaborate experimental toolbox to assess B cell biology, means to study FRC immunobiology are scarce, leaving BRC function almost entirely inferred from B cell perturbation studies 6, 7, 8, 9, 10, 11, 12. Within the B cell follicle (BF), Cxcl13-expressing B cell zone RCs (BRCs) steer B cell, antigen and leukocyte encounters thereby increasing germinal center (GC) efficiency 5. In the context of secondary lymphoid organs (SLOs), fibroblastic reticular cells (FRCs) form immune-supportive niches that are sustained throughout the steady state and during adaptive immune cell priming 2, 3, 4. Tissue homeostasis is defined as the regulated state of a tissue where supportive cells form optimized microenvironments to fulfill a tissue’s primary functions 1. Our data reveal that a canonical set of immune cell-provided cues enforce bidirectional signaling programs that sustain functional BRC niches across lymphoid organs and species, thereby securing efficient humoral immunity. As well as BRC-produced niche factors, immune cell-driven BRC differentiation and activation programs governed the convergence of shared BRC subsets, overwriting tissue-specific gene signatures. In addition to the major BRC subsets underpinning the follicle, including follicular dendritic cells, PI16 + RCs were present across organs and species. Here we dissected the BRC landscape and immune cell interactome in human and murine lymphoid organs.
However, a comprehensive understanding of systemic humoral immunity is hampered by the lack of knowledge of global BRC sustenance, function and major pathways controlling BRC–immune cell interactions. B cell zone reticular cells (BRCs) form stable microenvironments that direct efficient humoral immunity with B cell priming and memory maintenance being orchestrated across lymphoid organs.
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