B cells enhance early innate immune responses during bacterial sepsis
Open Access
- 11 July 2011
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 208 (8), 1673-1682
- https://doi.org/10.1084/jem.20101715
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.Keywords
This publication has 42 references indexed in Scilit:
- Type I IFN enhances follicular B cell contribution to the T cell–independent antibody responseThe Journal of Experimental Medicine, 2010
- Memory CD4+ T cells induce innate responses independently of pathogenNature Medicine, 2010
- Critical role of IRF-5 in regulation of B-cell differentiationProceedings of the National Academy of Sciences of the United States of America, 2010
- Type I interferon signaling in hematopoietic cells is required for survival in mouse polymicrobial sepsis by regulating CXCL10The Journal of Experimental Medicine, 2010
- B cell–intrinsic TLR signals amplify but are not required for humoral immunityThe Journal of Experimental Medicine, 2007
- Adaptive immune cells temper initial innate responsesNature Medicine, 2007
- MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsisThe Journal of Experimental Medicine, 2007
- Type I interferons protect neonates from acute inflammation through interleukin 10–producing B cellsThe Journal of Experimental Medicine, 2007
- Division and differentiation of natural antibody-producing cells in mouse spleenProceedings of the National Academy of Sciences of the United States of America, 2007
- Toll-like receptor control of the adaptive immune responsesNature Immunology, 2004