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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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Identification of IRA B cells after airway challenge. (A) Identification of IRA B cells in the lung 2 d after LPS i.n. challenge. A representative dot plot of n > 5 is shown. (B) Enumeration of IRA B cells in different organs in steady-state and after LPS challenge (n = 4/group). (C) Enumeration as percentage increase (n = 4). Relevant data are presented as mean ± SD and tested by ANOVA; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
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fig3: Identification of IRA B cells after airway challenge. (A) Identification of IRA B cells in the lung 2 d after LPS i.n. challenge. A representative dot plot of n > 5 is shown. (B) Enumeration of IRA B cells in different organs in steady-state and after LPS challenge (n = 4/group). (C) Enumeration as percentage increase (n = 4). Relevant data are presented as mean ± SD and tested by ANOVA; *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Mentions: The in vitro generation of IRA B cells from serosal B1a B cells led us to test whether IRA B cells can arise in the airways in vivo. We delivered LPS intranasally (i.n.) to WT mice and profiled the appearance of IRA B cells in various compartments 1 and 2 d later. Absolute IRA B cell numbers were highest in the lung and pleural space 2 d after LPS injection, with small numbers of IRA B cells accumulating in the bronchoalveolar lavage (BAL) and negligible numbers accumulating in both the lung-draining LN and blood at any point in time (Fig. 3, A and B). Expressing the increase of IRA B cells as a percentage of total B cells revealed dramatic increases in the pleural space, lung, and BAL (Fig. 3 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)

Identification of IRA B cells after airway challenge. (A) Identification of IRA B cells in the lung 2 d after LPS i.n. challenge. A representative dot plot of n > 5 is shown. (B) Enumeration of IRA B cells in different organs in steady-state and after LPS challenge (n = 4/group). (C) Enumeration as percentage increase (n = 4). Relevant data are presented as mean ± SD and tested by ANOVA; *, 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

fig3: Identification of IRA B cells after airway challenge. (A) Identification of IRA B cells in the lung 2 d after LPS i.n. challenge. A representative dot plot of n > 5 is shown. (B) Enumeration of IRA B cells in different organs in steady-state and after LPS challenge (n = 4/group). (C) Enumeration as percentage increase (n = 4). Relevant data are presented as mean ± SD and tested by ANOVA; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Mentions: The in vitro generation of IRA B cells from serosal B1a B cells led us to test whether IRA B cells can arise in the airways in vivo. We delivered LPS intranasally (i.n.) to WT mice and profiled the appearance of IRA B cells in various compartments 1 and 2 d later. Absolute IRA B cell numbers were highest in the lung and pleural space 2 d after LPS injection, with small numbers of IRA B cells accumulating in the bronchoalveolar lavage (BAL) and negligible numbers accumulating in both the lung-draining LN and blood at any point in time (Fig. 3, A and B). Expressing the increase of IRA B cells as a percentage of total B cells revealed dramatic increases in the pleural space, lung, and BAL (Fig. 3 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