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Transinteractome analysis reveals distinct niche requirements for isotype-based plasma cell subsets in the bone marrow |
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| Authors: | Amélie Bonaud Pierre Larraufie Mélanie Khamyath Ugo Szachnowski Shaun M. Flint Nadège Brunel-Meunier François Delhommeau Annie Munier Tapio Lönnberg Claire Toffano-Nioche Daniel Gautheret Karl Balabanian Marion Espéli |
| Affiliation: | 1. Université Paris Cité, Institut de Recherche Saint-Louis, INSERM U1160, Paris, France OPALE Carnot Institute, Hôpital St-Louis, Paris, France;2. Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France;3. Université Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, Clamart, France Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France;4. Université Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, Clamart, France;5. Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), AP-HP, Saint-Antoine Hospital, Paris, France;6. Sorbonne Université—INSERM UMRS_938, Centre de Recherche Saint-Antoine (CRSA), Plateforme de Cytométrie CISA, Paris, France;7. European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK;8. Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France;9. Université Paris Cité, Institut de Recherche Saint-Louis, INSERM U1160, Paris, France |
| Abstract: | Bone marrow (BM) long-lived plasma cells (PCs) are essential for long-term protection against infection, and their persistence within this organ relies on interactions with Cxcl12-expressing stromal cells that are still not clearly identified. Here, using single cell RNAseq and in silico transinteractome analyses, we identified Leptin receptor positive (LepR+) mesenchymal cells as the stromal cell subset most likely to interact with PCs within the BM. Moreover, we demonstrated that depending on the isotype they express, PCs may use different sets of integrins and adhesion molecules to interact with these stromal cells. Altogether, our results constitute an unprecedented characterization of PC subset stromal niches and open new avenues for the specific targeting of BM PCs based on their isotype. |
| Keywords: | Plasma cell Bone marrow Niche Stromal cell Transinteractome |