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Nat Immunol. 2014 Apr;15(4):354-64. doi: 10.1038/ni.2830. Epub 2014 Feb 23.

Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells.

Author information

  • 11] Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain. [2].
  • 21] Laboratory for Mucosal Immunity, RIKEN Center for Integrative Medical Sciences, RIKEN Yokohama, Yokohama, Japan. [2].
  • 3Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
  • 4Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • 5Immunology Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • 6Department of Pathology, Hospital del Mar, Universitat Autònoma de Barcelona and Universitat Pompeu Fabra, Barcelona, Spain.
  • 7Immunology Service, Hospital Clínic of Barcelona, Barcelona, Spain.
  • 81] Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Immunology Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • 9Laboratory for Mucosal Immunity, RIKEN Center for Integrative Medical Sciences, RIKEN Yokohama, Yokohama, Japan.
  • 101] Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain. [2] Immunology Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [3] Catalan Institute for Research and Advanced Studies, Barcelona Biomedical Research Park, Barcelona, Spain.

Abstract

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 RORγt(+) 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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PMID:
24562309
[PubMed - indexed for MEDLINE]
PMCID:
PMC4005806
Free PMC Article
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