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Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis.

Weber GF, Chousterman BG, Hilgendorf I, Robbins CS, Theurl I, Gerhardt LM, Iwamoto Y, Quach TD, Ali M, Chen JW, Rothstein TL, Nahrendorf M, Weissleder R, Swirski FK - J. Exp. Med. (2014)

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.

View Article: PubMed Central - HTML - PubMed

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 fswirski@mgh.harvard.edu georg.weber@uniklinikum-dresden.de.

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The pleural space is a reservoir of lung-infiltrating B1a B cells. (A) Cartoon depicting the ICAPS model. After skin incision, a small catheter can be navigated through the intercostal space and placed in the pleural space. (B) Preoperative: (i and ii) CT scans before insertion of the catheter. Intraoperative: (iii and iv) CT scans immediately after insertion of the catheter. (v and vi) CT scans after injection of 300 µl Iopamidol iodine CT contrast agent. Postoperative: (vii and viii) CT scans 10 min after the catheter was removed. There were no signs of injection into lung parenchyma, pneumothorax, or leakage (top row of CT scans: axial view; bottom rows of CT scans: sagittal view; arrows denote the tip of the catheter; stars donate the injected Iopamidol iodine CT contrast agent). (C) Intrapleural (i.e., by ICAPS) transfer of GFP+ serosal cells. Cells were transferred into WT mice which were sacrificed 10 min after transfer. Data show transferred cells in the pleural space, BAL, blood, lung, bone marrow, and spleen. (D) Unsorted GFP+ serosal cells were adoptively transferred to the pleural or peritoneal spaces of WT mice that received pulmonary LPS challenge. Data show profile of lung accumulation in recipients 2 d after transfer. A representative experiment of n = 5 is shown. (E) Enumeration of CD19+ and CD19− cells accumulating in the lung and spleen after intrapleural or intraperitoneal transfer of unsorted GFP+ serosal cells. A representative enumeration of n = 5 is shown. (F) Intrapleural adoptive transfer of serosal B1a GFP+ cells. Data show frequency of adoptively transferred (GFP+) cells in the lung, pleural space, and blood 2 d after pulmonary LPS challenge. A representative dot plot from n = 4 is shown. (G) Fluorescence microscopy of lung tissue 2 d after intrapleural adoptive transfer of sorted GFP+ serosal B1a cells (bars: overview, 20 µm; inset, 10 µm).
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fig7: The pleural space is a reservoir of lung-infiltrating B1a B cells. (A) Cartoon depicting the ICAPS model. After skin incision, a small catheter can be navigated through the intercostal space and placed in the pleural space. (B) Preoperative: (i and ii) CT scans before insertion of the catheter. Intraoperative: (iii and iv) CT scans immediately after insertion of the catheter. (v and vi) CT scans after injection of 300 µl Iopamidol iodine CT contrast agent. Postoperative: (vii and viii) CT scans 10 min after the catheter was removed. There were no signs of injection into lung parenchyma, pneumothorax, or leakage (top row of CT scans: axial view; bottom rows of CT scans: sagittal view; arrows denote the tip of the catheter; stars donate the injected Iopamidol iodine CT contrast agent). (C) Intrapleural (i.e., by ICAPS) transfer of GFP+ serosal cells. Cells were transferred into WT mice which were sacrificed 10 min after transfer. Data show transferred cells in the pleural space, BAL, blood, lung, bone marrow, and spleen. (D) Unsorted GFP+ serosal cells were adoptively transferred to the pleural or peritoneal spaces of WT mice that received pulmonary LPS challenge. Data show profile of lung accumulation in recipients 2 d after transfer. A representative experiment of n = 5 is shown. (E) Enumeration of CD19+ and CD19− cells accumulating in the lung and spleen after intrapleural or intraperitoneal transfer of unsorted GFP+ serosal cells. A representative enumeration of n = 5 is shown. (F) Intrapleural adoptive transfer of serosal B1a GFP+ cells. Data show frequency of adoptively transferred (GFP+) cells in the lung, pleural space, and blood 2 d after pulmonary LPS challenge. A representative dot plot from n = 4 is shown. (G) Fluorescence microscopy of lung tissue 2 d after intrapleural adoptive transfer of sorted GFP+ serosal B1a cells (bars: overview, 20 µm; inset, 10 µm).

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).


Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis.

Weber GF, Chousterman BG, Hilgendorf I, Robbins CS, Theurl I, Gerhardt LM, Iwamoto Y, Quach TD, Ali M, Chen JW, Rothstein TL, Nahrendorf M, Weissleder R, Swirski FK - J. Exp. Med. (2014)

The pleural space is a reservoir of lung-infiltrating B1a B cells. (A) Cartoon depicting the ICAPS model. After skin incision, a small catheter can be navigated through the intercostal space and placed in the pleural space. (B) Preoperative: (i and ii) CT scans before insertion of the catheter. Intraoperative: (iii and iv) CT scans immediately after insertion of the catheter. (v and vi) CT scans after injection of 300 µl Iopamidol iodine CT contrast agent. Postoperative: (vii and viii) CT scans 10 min after the catheter was removed. There were no signs of injection into lung parenchyma, pneumothorax, or leakage (top row of CT scans: axial view; bottom rows of CT scans: sagittal view; arrows denote the tip of the catheter; stars donate the injected Iopamidol iodine CT contrast agent). (C) Intrapleural (i.e., by ICAPS) transfer of GFP+ serosal cells. Cells were transferred into WT mice which were sacrificed 10 min after transfer. Data show transferred cells in the pleural space, BAL, blood, lung, bone marrow, and spleen. (D) Unsorted GFP+ serosal cells were adoptively transferred to the pleural or peritoneal spaces of WT mice that received pulmonary LPS challenge. Data show profile of lung accumulation in recipients 2 d after transfer. A representative experiment of n = 5 is shown. (E) Enumeration of CD19+ and CD19− cells accumulating in the lung and spleen after intrapleural or intraperitoneal transfer of unsorted GFP+ serosal cells. A representative enumeration of n = 5 is shown. (F) Intrapleural adoptive transfer of serosal B1a GFP+ cells. Data show frequency of adoptively transferred (GFP+) cells in the lung, pleural space, and blood 2 d after pulmonary LPS challenge. A representative dot plot from n = 4 is shown. (G) Fluorescence microscopy of lung tissue 2 d after intrapleural adoptive transfer of sorted GFP+ serosal B1a cells (bars: overview, 20 µm; inset, 10 µm).
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fig7: The pleural space is a reservoir of lung-infiltrating B1a B cells. (A) Cartoon depicting the ICAPS model. After skin incision, a small catheter can be navigated through the intercostal space and placed in the pleural space. (B) Preoperative: (i and ii) CT scans before insertion of the catheter. Intraoperative: (iii and iv) CT scans immediately after insertion of the catheter. (v and vi) CT scans after injection of 300 µl Iopamidol iodine CT contrast agent. Postoperative: (vii and viii) CT scans 10 min after the catheter was removed. There were no signs of injection into lung parenchyma, pneumothorax, or leakage (top row of CT scans: axial view; bottom rows of CT scans: sagittal view; arrows denote the tip of the catheter; stars donate the injected Iopamidol iodine CT contrast agent). (C) Intrapleural (i.e., by ICAPS) transfer of GFP+ serosal cells. Cells were transferred into WT mice which were sacrificed 10 min after transfer. Data show transferred cells in the pleural space, BAL, blood, lung, bone marrow, and spleen. (D) Unsorted GFP+ serosal cells were adoptively transferred to the pleural or peritoneal spaces of WT mice that received pulmonary LPS challenge. Data show profile of lung accumulation in recipients 2 d after transfer. A representative experiment of n = 5 is shown. (E) Enumeration of CD19+ and CD19− cells accumulating in the lung and spleen after intrapleural or intraperitoneal transfer of unsorted GFP+ serosal cells. A representative enumeration of n = 5 is shown. (F) Intrapleural adoptive transfer of serosal B1a GFP+ cells. Data show frequency of adoptively transferred (GFP+) cells in the lung, pleural space, and blood 2 d after pulmonary LPS challenge. A representative dot plot from n = 4 is shown. (G) Fluorescence microscopy of lung tissue 2 d after intrapleural adoptive transfer of sorted GFP+ serosal B1a cells (bars: overview, 20 µm; inset, 10 µm).
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).

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.

View Article: PubMed Central - HTML - PubMed

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 fswirski@mgh.harvard.edu georg.weber@uniklinikum-dresden.de.

Show MeSH
Related in: MedlinePlus