Home LiteratureArticle Details
PMID: 22245738 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Innate response activator B cells protect against microbial sepsis.

Science (New York, N.Y.) ·Vol. 335 ·No. 6068 ·2012-02-03 ·Pages 597-601

Rauch PJ, Chudnovskiy A, Robbins CS, Weber GF, Etzrodt M, Hilgendorf I, Tiglao E, Figueiredo JL, Iwamoto Y, Theurl I, Gorbatov R, Waring MT, Chicoine AT, Mouded M, Pittet MJ, Nahrendorf M, Weissleder R, Swirski FK

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.

MeSH Terms
Animals B-Lymphocyte Subsets/immunology,metabolism Cell Lineage Cell Separation Escherichia coli Infections/immunology Female Flow Cytometry Granulocyte-Macrophage Colony-Stimulating Factor/immunology,metabolism Immunity, Innate Immunoglobulin M/metabolism Immunophenotyping Integrin alpha4beta1/immunology,metabolism Lipopolysaccharides Lymphocyte Activation Lymphocyte Function-Associated Antigen-1/immunology,metabolism Mice Mice, Inbred C57BL Parabiosis Peritonitis/immunology Sepsis/immunology Shock, Septic/immunology Spleen/immunology Toll-Like Receptor 4/immunology
Chemicals
Immunoglobulin M Integrin alpha4beta1 Lipopolysaccharides Lymphocyte Function-Associated Antigen-1 Tlr4 protein, mouse Toll-Like Receptor 4 Granulocyte-Macrophage Colony-Stimulating Factor
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Rauch Philipp J
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Chudnovskiy Aleksey
Robbins Clinton S
Weber Georg F
Etzrodt Martin
Hilgendorf Ingo
Tiglao Elizabeth
Figueiredo Jose-Luiz
Iwamoto Yoshiko
Theurl Igor
Gorbatov Rostic
Waring Michael T
Chicoine Adam T
Mouded Majd
Pittet Mikael J
Nahrendorf Matthias
Weissleder Ralph
Swirski Filip K
References (34)
34 references, click to expand
  1. Murine marrow cellularity and the concept of stem cell competition: geographic and quantitative determinants in stem cell biology.
    Leukemia. 2004 Mar;18(3):575-83 PMID: 14749701
  2. Peritoneal cavity B cells are precursors of splenic IgM natural antibody-producing cells.
    J Immunol. 2003 Nov 15;171(10):5406-14 PMID: 14607944
  3. Increased tolerance to endotoxin by granulocyte-macrophage colony-stimulating factor-deficient mice.
    J Immunol. 1997 Aug 1;159(3):1412-7 PMID: 9233638
  4. Receptor clearance obscures the magnitude of granulocyte-macrophage colony-stimulating factor responses in mice to endotoxin or local infections.
    Blood. 1999 Mar 1;93(5):1579-85 PMID: 10029586
  5. The follicular versus marginal zone B lymphocyte cell fate decision.
    Nat Rev Immunol. 2009 Nov;9(11):767-77 PMID: 19855403
  6. Marginal-zone B cells.
    Nat Rev Immunol. 2002 May;2(5):323-35 PMID: 12033738
  7. Q-Gene: processing quantitative real-time RT-PCR data.
    Bioinformatics. 2003 Jul 22;19(11):1439-40 PMID: 12874059
  8. GenePattern 2.0.
    Nat Genet. 2006 May;38(5):500-1 PMID: 16642009
  9. Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation.
    J Immunol. 2001 Dec 15;167(12):6834-40 PMID: 11739500
  10. Granulocyte-macrophage colony-stimulating factor as an autocrine survival factor for mature normal and malignant B lymphocytes.
    J Immunol. 2000 Apr 1;164(7):3887-93 PMID: 10725751
  11. A new non-linear normalization method for reducing variability in DNA microarray experiments.
    Genome Biol. 2002 Aug 30;3(9):research0048 PMID: 12225587
  12. Immunotherapy for sepsis--a new approach against an ancient foe.
    N Engl J Med. 2010 Jul 1;363(1):87-9 PMID: 20592301
  13. GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival.
    J Exp Med. 2008 Sep 29;205(10):2281-94 PMID: 18779348
  14. The immunopathogenesis of sepsis.
    Nature. 2002 Dec 19-26;420(6917):885-91 PMID: 12490963
  15. Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice.
    Nature. 1995 Jul 27;376(6538):352-5 PMID: 7543183
  16. A small CD11b(+) human B1 cell subpopulation stimulates T cells and is expanded in lupus.
    J Exp Med. 2011 Dec 19;208(13):2591-8 PMID: 22110167
  17. Cluster analysis and display of genome-wide expression patterns.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 PMID: 9843981
  18. The epidemiology of sepsis in the United States from 1979 through 2000.
    N Engl J Med. 2003 Apr 17;348(16):1546-54 PMID: 12700374
  19. Structure and function of the spleen.
    Nat Rev Immunol. 2005 Aug;5(8):606-16 PMID: 16056254
  20. Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow.
    J Exp Med. 2001 Oct 15;194(8):1151-64 PMID: 11602643
  21. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene.
    Nature. 1991 Apr 4;350(6317):423-6 PMID: 1901381
  22. Regulation of B1 cell migration by signals through Toll-like receptors.
    J Exp Med. 2006 Oct 30;203(11):2541-50 PMID: 17060475
  23. B lymphocytes: how they develop and function.
    Blood. 2008 Sep 1;112(5):1570-80 PMID: 18725575
  24. Granulocyte macrophage colony-stimulating factor improves survival in two models of gut-derived sepsis by improving gut barrier function and modulating bacterial clearance.
    Ann Surg. 1994 Jul;220(1):68-76 PMID: 8024361
  25. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway.
    Science. 2001 Sep 14;293(5537):2111-4 PMID: 11509691
  26. Integrin-mediated long-term B cell retention in the splenic marginal zone.
    Science. 2002 Jul 19;297(5580):409-12 PMID: 12130787
  27. New perspectives in B-1 B cell development and function.
    Trends Immunol. 2006 Sep;27(9):428-33 PMID: 16861037
  28. Immunodesign of experimental sepsis by cecal ligation and puncture.
    Nat Protoc. 2009;4(1):31-6 PMID: 19131954
  29. Colony-stimulating factors in inflammation and autoimmunity.
    Nat Rev Immunol. 2008 Jul;8(7):533-44 PMID: 18551128
  30. Identification of splenic reservoir monocytes and their deployment to inflammatory sites.
    Science. 2009 Jul 31;325(5940):612-6 PMID: 19644120
  31. Animal models of sepsis and sepsis-induced kidney injury.
    J Clin Invest. 2009 Oct;119(10):2868-78 PMID: 19805915
  32. Principal components analysis to summarize microarray experiments: application to sporulation time series.
    Pac Symp Biocomput. 2000;:455-66 PMID: 10902193
  33. Peripheral B cell subsets.
    Curr Opin Immunol. 2008 Apr;20(2):149-57 PMID: 18434123
  34. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses.
    Immunity. 2008 May;28(5):639-50 PMID: 18482568
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1215173
Published
2012-02-03
Epub
2012-00-12
Pages
597-601
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3279743
Subset
IM
Grants
NHLBI NIH HHS · R01 HL095612 · United States
NCI NIH HHS · R24 CA69246 · United States
PHS HHS · P01-A154904 · United States
NCRR NIH HHS · S10 RR026360 · United States
NHLBI NIH HHS · 1R01HL095612 · United States
NCI NIH HHS · P50 CA86355 · United States
NHLBI NIH HHS · U01 HL080731-04 · United States
NCI NIH HHS · P50 CA086355-11 · United States
NHLBI NIH HHS · U01 HL080731 · United States
NCI NIH HHS · P01 CA069246 · United States
NHLBI NIH HHS · R01 HL095612-03 · United States
NCI NIH HHS · P50 CA086355 · United States
Databases
GEO
GSE32372
External Links
PubMed source DOI: 10.1126/science.1215173 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2