Conserved stromal-immune cell circuits secure B cell homeostasis and function.
Journal Paper/Review - May 18, 2023
Lütge Mechthild, De Martin Angelina, Gil Cruz Cristina, Perez Shibayama Christian, Stanossek Yves, Onder Lucas, Cheng Hung-Wei, Kurz Lisa, Cadosch Nadine, Soneson Charlotte, Robinson Mark D, Stöckli Sandro, Ludewig Burkhard, Pikor Natalia
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. 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. Here we dissected the BRC landscape and immune cell interactome in human and murine lymphoid organs. In addition to the major BRC subsets underpinning the follicle, including follicular dendritic cells, PI16 RCs were present across organs and species. 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. 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.