title: Innate response activator B cells protect against microbial sepsis.
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.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Philipp J
authors.initials: PJ
authors.lastname: Rauch
authors.forename: Aleksey
authors.initials: A
authors.lastname: Chudnovskiy
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Robbins
authors.forename: Georg F
authors.initials: GF
authors.lastname: Weber
authors.forename: Martin
authors.initials: M
authors.lastname: Etzrodt
authors.forename: Ingo
authors.initials: I
authors.lastname: Hilgendorf
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tiglao
authors.forename: Jose-Luiz
authors.initials: JL
authors.lastname: Figueiredo
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Igor
authors.initials: I
authors.lastname: Theurl
authors.forename: Rostic
authors.initials: R
authors.lastname: Gorbatov
authors.forename: Michael T
authors.initials: MT
authors.lastname: Waring
authors.forename: Adam T
authors.initials: AT
authors.lastname: Chicoine
authors.forename: Majd
authors.initials: M
authors.lastname: Mouded
authors.forename: Mikael J
authors.initials: MJ
authors.lastname: Pittet
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D019070:Cell Lineage; D002469:Cell Separation; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate; D007075:Immunoglobulin M / Q000378:metabolism; D016130:Immunophenotyping; D039041:Integrin alpha4beta1 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010227:Parabiosis; D010538:Peritonitis / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology; D013154:Spleen / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D007075:Immunoglobulin M; D039041:Integrin alpha4beta1; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor