How and where natural IgM are secreted is not fully understood. These serous cavities constitute important reservoirs of innate-like B-cell subsets, also called B1 cells, the major innate function of which is to ensure early immune protection from infection by rapid secretion of natural IgM. The serous membranes covering the viscera and the wall of the body cavities define three fluid-filled cavities: the peritoneal, pleural and pericardial cavities. 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. Moreover, lung inflammation leads to increased IL-5 production by type 2 cytokine-producing innate lymphoid cells (ILC2) in the FALC. However, B1 cells are not the direct target of IL-33, which instead requires IL-5 for activation. IL-33 produced by FALC stroma is crucial for pleural B1-cell activation and local IgM secretion. 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. 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. Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities.