title: Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis.
abstract: Pneumonia is a major cause of mortality worldwide and a serious problem in critical care medicine, but the immunophysiological processes that confer either protection or morbidity are not completely understood. 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 process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. 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.
authors.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.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Weber
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Chousterman
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: Ingo
authors.initials: I
authors.lastname: Hilgendorf
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Robbins
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: Igor
authors.initials: I
authors.lastname: Theurl
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: Louisa M S
authors.initials: LM
authors.lastname: Gerhardt
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030.
authors.forename: Tam D
authors.initials: TD
authors.lastname: Quach
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: John W
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Rothstein
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 fswirski@mgh.harvard.edu georg.weber@uniklinikum-dresden.de.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
mesh_terms: D000328:Adult; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007075:Immunoglobulin M / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010994:Pleura / Q000276:immunology* / Q000378:metabolism; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D007075:Immunoglobulin M; D016178:Granulocyte-Macrophage Colony-Stimulating Factor