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Suchanek, Ondrej; Ferdinand, John R; Tuong, Zewen K; Wijeyesinghe, Sathi; Chandra, Anita; Clauder, Ann-Katrin; Almeida, Larissa N; Clare, Simon; Harcourt, Katherine; Ward, Christopher J; Bashford-Rogers, Rachael; Lawley, Trevor; Manz, Rudolf A; Okkenhaug, Klaus; Masopust, David; Clatworthy, Menna R
Nature communications, 11/2023, Volume: 14, Issue: 1Journal Article
B cells play a central role in humoral immunity but also have antibody-independent functions. Studies to date have focused on B cells in blood and secondary lymphoid organs but whether B cells reside in non-lymphoid organs (NLO) in homeostasis is unknown. Here we identify, using intravenous labeling and parabiosis, a bona-fide tissue-resident B cell population in lung, liver, kidney and urinary bladder, a substantial proportion of which are B-1a cells. Tissue-resident B cells are present in neonatal tissues and also in germ-free mice NLOs, albeit in lower numbers than in specific pathogen-free mice and following co-housing with 'pet-store' mice. They spatially co-localise with macrophages and regulate their polarization and function, promoting an anti-inflammatory phenotype, in-part via interleukin-10 production, with effects on bacterial clearance during urinary tract infection. Thus, our data reveal a critical role for tissue-resident B cells in determining the homeostatic 'inflammatory set-point' of myeloid cells, with important consequences for tissue immunity.
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