Journal
NATURE IMMUNOLOGY
Volume 15, Issue 4, Pages 354-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2830
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Funding
- European Research Council [ERC-2011-ADG-20110310]
- Ministerio de Economia y Competitividad, Gobierno de Espana [SAF2011-25241]
- European Commission [PIRG-08-GA-2010-276928]
- US National Institutes of Health [R01 AI74378, R01 AI57653, U01 AI95613, U01 AI95776 IOF, P01 AI61093, U19 096187]
- Ministry of Education, Culture, Sport, Science and Technology of Japan [25293118]
- Integrative Medical Sciences-Research Center for Allergy and Immunology
- ICREA Funding Source: Custom
- Grants-in-Aid for Scientific Research [25293118] Funding Source: KAKEN
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Innate lymphoid cells (ILCs) regulate stromal cells, epithelial cells and cells of the immune system, but their effect on B cells remains unclear. Here we identified ROR gamma t(+) ILCs near the marginal zone (MZ), a splenic compartment that contains innate-like B cells highly responsive to circulating T cell-independent (TI) antigens. Splenic ILCs established bidirectional crosstalk with MAdCAM-1(+) marginal reticular cells by providing tumor-necrosis factor (TNF) and lymphotoxin, and they stimulated MZ B cells via B cell-activation factor (BAFF), the ligand of the costimulatory receptor CD40 (CD40L) and the Notch ligand Delta-like 1 (DLL1). Splenic ILCs further helped MZ B cells and their plasma-cell progeny by coopting neutrophils through release of the cytokine GM-CSF. Consequently, depletion of ILCs impaired both pre- and post-immune TI antibody responses. Thus, ILCs integrate stromal and myeloid signals to orchestrate innate-like antibody production at the interface between the immune system and circulatory system.
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