title: Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation.
abstract: Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about the physiological cues that activate FALCs in the pleural cavity and more generally the mechanisms controlling B-cell activation in FALCs. Here we show, using separate models of pleural nematode infection with Litomosoides sigmodontis and Altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity rapidly activates mediastinal and pericardial FALCs. IL-33 produced by FALC stroma is crucial for pleural B1-cell activation and local IgM secretion. However, B1 cells are not the direct target of IL-33, which instead requires IL-5 for activation. Moreover, lung inflammation leads to increased IL-5 production by type 2 cytokine-producing innate lymphoid cells (ILC2) in the FALC. These findings reveal a link between inflammation, IL-33 release by FALC stromal cells, ILC2 activation and pleural B-cell activation in FALCs, resulting in local and antigen-specific IgM production.
authors: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, Scotland EH9 3FL, UK.|Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland EH16 4TJ, UK.
authors: Lucy H
authors: LH
authors: Jackson-Jones
authors: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, Scotland EH9 3FL, UK.
authors: Sheelagh M
authors: SM
authors: Duncan
authors: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland EH16 4TJ, UK.
authors: Marlène S
authors: MS
authors: Magalhaes
authors: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, Scotland EH9 3FL, UK.
authors: Sharon M
authors: SM
authors: Campbell
authors: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, Scotland EH9 3FL, UK.
authors: Rick M
authors: RM
authors: Maizels
authors: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, Scotland EH9 3FL, UK.|Centre for Inflammation Research, University of Edinburgh, Edinburgh, Scotland EH16 4TJ, UK.
authors: Henry J
authors: HJ
authors: McSorley
authors: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, Scotland EH9 3FL, UK.|Faculty of Biology, Medicine &Health, University of Manchester, AV Hill Building, Manchester M13 9PT, UK.
authors: Judith E
authors: JE
authors: Allen
authors: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland EH16 4TJ, UK.
authors: Cécile
authors: C
authors: Bénézech
mesh_terms: D000528:Alternaria / Q000276:immunology*; D060487:Alternariosis / Q000276:immunology / Q000469:parasitology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005368:Filariasis / Q000276:immunology / Q000469:parasitology; D005370:Filarioidea / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D000067596:Interleukin-33 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology*
chemical_list: D007075:Immunoglobulin M; D000067596:Interleukin-33; D015848:Interleukin-5