Conserved stromal-immune cell circuits secure B cell homeostasis and function.
Mechthild LütgeAngelina De MartinCristina Gil-CruzChristian Perez-ShibayamaYves StanossekLucas OnderHung-Wei ChengLisa KurzNadine CadoschCharlotte SonesonMark D RobinsonSandro J StoeckliBurkhard LudewigNatalia Barbara PikorPublished in: Nature immunology (2023)
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.
Keyphrases
- immune response
- dendritic cells
- genome wide
- endothelial cells
- public health
- peripheral blood
- induced apoptosis
- single cell
- transcription factor
- gene expression
- bone marrow
- dna methylation
- oxidative stress
- working memory
- cell death
- machine learning
- electronic health record
- copy number
- cell proliferation
- regulatory t cells
- genetic diversity
- data analysis