IgM antibodies provide vital protection early during infection

IgM antibodies provide vital protection early during infection

Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation

IgM antibodies provide vital protection early during infection. In this article, published in Nature Communications, we show that special fat tissues found close to the lungs and heart are critical immune sites allowing early secretion of IgM during lung and pleural infection.

Nature Communications Volume: 7, Article number: 12651 DOI: doi:10.1038/ncomms12651

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.

Fat-associated lymphoid clusters of the pericardium and mediastinum support the proliferation of B cells (red) and the production of parasite specific IgM antibodies (green)