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Science 335 (6068): 597-601

Copyright © 2012 by the American Association for the Advancement of Science

Innate Response Activator B Cells Protect Against Microbial Sepsis

Philipp J. Rauch,1,* Aleksey Chudnovskiy,1,* Clinton S. Robbins,1,*,{dagger} Georg F. Weber,1 Martin Etzrodt,1 Ingo Hilgendorf,1,6 Elizabeth Tiglao,1 Jose-Luiz Figueiredo,1 Yoshiko Iwamoto,1 Igor Theurl,1,3,7 Rostic Gorbatov,1 Michael T. Waring,4 Adam T. Chicoine,4 Majd Mouded,5 Mikael J. Pittet,1 Matthias Nahrendorf,1 Ralph Weissleder,1,2 Filip K. Swirski1,{dagger}

Abstract: Recognition and clearance of a bacterial infection are a fundamental properties of innate immunity. Here, we describe an effector B cell population that protects against microbial sepsis. Innate response activator (IRA) B cells are phenotypically and functionally distinct, develop and diverge from B1a B cells, depend on pattern-recognition receptors, and produce granulocyte-macrophage colony-stimulating factor. Specific deletion of IRA B cell activity impairs bacterial clearance, elicits a cytokine storm, and precipitates septic shock. These observations enrich our understanding of innate immunity, position IRA B cells as gatekeepers of bacterial infection, and identify new treatment avenues for infectious diseases.

1 Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
2 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
3 Program in Membrane Biology and Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
4 Ragon Institute Imaging Core, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
5 Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
6 Department of Cardiology, University Hospital Freiburg, 79106 Freiburg, Germany.
7 Department of General Internal Medicine, Clinical Immunology and Infectious Diseases, University Hospital of Innsbruck, A-6020 Innsbruck, Austria.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: fswirski{at}mgh.harvard.edu (F.K.S.); robbins.clinton{at}mgh.harvard.edu (C.S.R.)


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