Limits...
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.

Show MeSH

Related in: MedlinePlus

Enhanced inflammation but attenuated IgM after E. coli airway infection in the absence of IRA B cells. (A) IgM levels detected by ELISA in serum, BAL, and pleural space 9 h after E. coli infection (n = 6–10 mice). (B) Lung histology after E. coli infection. DAPI: blue; CD19: red; IgM: green; merge: yellow. Representative pictographs of n = 6–10 animals/group are shown (bars: overview, 100 µm; inset, 10 µm). Arrows indicate IgM+CD19+ cells. (C) Analysis of WT/µMT and GM/µMT mice after i.t. E. coli infection. Immunohistochemical staining for neutrophils in lung tissue and enumeration of neutrophils measured by counts of neutrophils per field of view. A representative slide of n = 6–10 is shown (bars, 400 µm). (D) Enumeration of neutrophils in blood and BAL (n = 6–10). (E) Analysis of the phagocytic capacity of neutrophils from the BAL of WT/µMT and GM/µMT mice. Shown are total cell numbers with phagocytosed Pkh26+ bacteria (n = 4). (F) Analysis of BAL levels for IL-1α, IL-6, TNF, and CXCL1 (n = 5–15 mice). Relevant data are presented as mean ± SD; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4042649&req=5

fig6: Enhanced inflammation but attenuated IgM after E. coli airway infection in the absence of IRA B cells. (A) IgM levels detected by ELISA in serum, BAL, and pleural space 9 h after E. coli infection (n = 6–10 mice). (B) Lung histology after E. coli infection. DAPI: blue; CD19: red; IgM: green; merge: yellow. Representative pictographs of n = 6–10 animals/group are shown (bars: overview, 100 µm; inset, 10 µm). Arrows indicate IgM+CD19+ cells. (C) Analysis of WT/µMT and GM/µMT mice after i.t. E. coli infection. Immunohistochemical staining for neutrophils in lung tissue and enumeration of neutrophils measured by counts of neutrophils per field of view. A representative slide of n = 6–10 is shown (bars, 400 µm). (D) Enumeration of neutrophils in blood and BAL (n = 6–10). (E) Analysis of the phagocytic capacity of neutrophils from the BAL of WT/µMT and GM/µMT mice. Shown are total cell numbers with phagocytosed Pkh26+ bacteria (n = 4). (F) Analysis of BAL levels for IL-1α, IL-6, TNF, and CXCL1 (n = 5–15 mice). Relevant data are presented as mean ± SD; *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Mentions: Having observed that B cell–derived GM-CSF protected against pneumonia, we next examined the mixed chimeras’ cellular and humoral response, particularly whether the absence of B cell–derived GM-CSF associates with impaired IgM production in vivo. In the steady-state, IgM was readily detectable, and its similar concentrations in GM/µMT and WT/µMT mice indicated that IRA B cells are dispensable to steady-state IgM production. After infection, control but not GM/µMT mice showed augmented IgM in the pleural space, lung, and serum, indicating impaired emergency IgM production in mice lacking IRA B cells (Fig. 6 A). Immunofluorescence microscopy showed lung B cells in GM/µMT mice to be weakly positive for IgM compared with controls (Fig. 6 B). The data suggest that B cell–derived GM-CSF is required for IgM production in vivo in response to lung infection.


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)

Enhanced inflammation but attenuated IgM after E. coli airway infection in the absence of IRA B cells. (A) IgM levels detected by ELISA in serum, BAL, and pleural space 9 h after E. coli infection (n = 6–10 mice). (B) Lung histology after E. coli infection. DAPI: blue; CD19: red; IgM: green; merge: yellow. Representative pictographs of n = 6–10 animals/group are shown (bars: overview, 100 µm; inset, 10 µm). Arrows indicate IgM+CD19+ cells. (C) Analysis of WT/µMT and GM/µMT mice after i.t. E. coli infection. Immunohistochemical staining for neutrophils in lung tissue and enumeration of neutrophils measured by counts of neutrophils per field of view. A representative slide of n = 6–10 is shown (bars, 400 µm). (D) Enumeration of neutrophils in blood and BAL (n = 6–10). (E) Analysis of the phagocytic capacity of neutrophils from the BAL of WT/µMT and GM/µMT mice. Shown are total cell numbers with phagocytosed Pkh26+ bacteria (n = 4). (F) Analysis of BAL levels for IL-1α, IL-6, TNF, and CXCL1 (n = 5–15 mice). Relevant data are presented as mean ± SD; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4042649&req=5

fig6: Enhanced inflammation but attenuated IgM after E. coli airway infection in the absence of IRA B cells. (A) IgM levels detected by ELISA in serum, BAL, and pleural space 9 h after E. coli infection (n = 6–10 mice). (B) Lung histology after E. coli infection. DAPI: blue; CD19: red; IgM: green; merge: yellow. Representative pictographs of n = 6–10 animals/group are shown (bars: overview, 100 µm; inset, 10 µm). Arrows indicate IgM+CD19+ cells. (C) Analysis of WT/µMT and GM/µMT mice after i.t. E. coli infection. Immunohistochemical staining for neutrophils in lung tissue and enumeration of neutrophils measured by counts of neutrophils per field of view. A representative slide of n = 6–10 is shown (bars, 400 µm). (D) Enumeration of neutrophils in blood and BAL (n = 6–10). (E) Analysis of the phagocytic capacity of neutrophils from the BAL of WT/µMT and GM/µMT mice. Shown are total cell numbers with phagocytosed Pkh26+ bacteria (n = 4). (F) Analysis of BAL levels for IL-1α, IL-6, TNF, and CXCL1 (n = 5–15 mice). Relevant data are presented as mean ± SD; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Mentions: Having observed that B cell–derived GM-CSF protected against pneumonia, we next examined the mixed chimeras’ cellular and humoral response, particularly whether the absence of B cell–derived GM-CSF associates with impaired IgM production in vivo. In the steady-state, IgM was readily detectable, and its similar concentrations in GM/µMT and WT/µMT mice indicated that IRA B cells are dispensable to steady-state IgM production. After infection, control but not GM/µMT mice showed augmented IgM in the pleural space, lung, and serum, indicating impaired emergency IgM production in mice lacking IRA B cells (Fig. 6 A). Immunofluorescence microscopy showed lung B cells in GM/µMT mice to be weakly positive for IgM compared with controls (Fig. 6 B). The data suggest that B cell–derived GM-CSF is required for IgM production in vivo in response to lung infection.

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