Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis.
Bottom Line: We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M (IgM).The strategic location of these cells, coupled with the capacity to produce GM-CSF-dependent IgM, ensures effective early frontline defense against bacteria invading the lungs.The study describes a previously unrecognized GM-CSF-IgM axis and positions IRA B cells as orchestrators of protective IgM immunity.
Affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Visceral, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany firstname.lastname@example.org email@example.com.Show MeSH
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Mentions: Coelomate animals contain peritoneal, pleural, and pericardial cavities that shield and support internal organs. The pleural cavity is the space between the outer parietal pleura attached to the chest wall and the inner visceral pleura that covers the lungs. Its primary purpose may be to aid lung function, as the pleural fluid allows the membranes to slide effortlessly during ventilation, but the space also contains immune cells such as macrophages and B cells. Such leukocyte location could be strategic; pleural cells may function as either sentinels against barrier-breaching or reservoirs for lung infiltration. Our observations that serosal B1a B cells can give rise to IRA B cells in vitro (Fig. 1 A); that IRA B cells arise in the pleural space/lung during airway infection (Fig. 3); and that B cell–derived GM-CSF controls IgM production in the airways (Fig. 6, A–C) prompted the hypothesis that the pleural space sources lung-infiltrating IgM-producing B cells in response to bacterial airway infection. To test this, we developed the intercostal approach of the pleural space (ICAPS) method (Fig. 7 A), in which a catheter is intercostally inserted into the organism’s thorax at a low angle to bypass the diaphragm and reduce the risk of puncturing the lung. When the catheter is removed, the intercostal muscles seal the puncture canal and prevent a pneumothorax. We confirmed the validity of this procedure by injecting a CT imaging contrast agent into the pleural space (Fig. 7 B) and transferring GFP+ leukocytes for in vivo fate mapping (Fig. 7 C).
Affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Visceral, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany firstname.lastname@example.org email@example.com.