B cells enhance early innate immune responses during bacterial sepsis

Kindra M. Kelly-Scumpia, Philip O. Scumpia, Jason S. Weinstein, Matthew J. Delano, Alex G. Cuenca, Dina C. Nacionales, James L. Wynn, Pui Y. Lee, Yutaro Kumagai, Philip A. Efron, Shizuo Akira, Clive Wasserfall, Mark A. Atkinson, Lyle L. Moldawer

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses to viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B cells in the early innate immune response during bacterial sepsis. We demonstrate that Rag1-/- mice display deficient early inflammatory responses and reduced survival during sepsis. Interestingly, B cell-deficient or anti-CD20 B cell-depleted mice, but not α/β T cell-deficient mice, display decreased inflammatory cytokine and chemokine production and reduced survival after sepsis. Both treatment of B cell-deficient mice with serum from wild-type (WT) mice and repletion of Rag1-/- mice with B cells improves sepsis survival, suggesting antibody-independent and antibody-dependent roles for B cells in the outcome to sepsis. During sepsis, marginal zone and follicular B cells are activated through type I interferon (IFN-I) receptor (IFN-α/β receptor [IFNAR]), and repleting Rag1-/- mice with WT, but not IFNAR-/-, B cells improves IFN-I-dependent and -independent early cytokine responses. Repleting B cell-deficient mice with the IFN-I-dependent chemokine, CXCL10 was also sufficient to improve sepsis survival. This study identifies a novel role for IFN-I-activated B cells in protective early innate immune responses during bacterial sepsis.

Original languageEnglish (US)
Pages (from-to)1673-1682
Number of pages10
JournalJournal of Experimental Medicine
Volume208
Issue number18
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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