• 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, and Lyle L Moldawer.
• Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA.
• J. Exp. Med. 2011 Aug 1;208(8):1673-82.

AbstractMicrobes 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.

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