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

Nat Immunol. 2014 Apr;15(4):354-364. doi: 10.1038/ni.2830. Epub 2014 Feb 23.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / blood
  • Antibody Formation*
  • Antigens, T-Independent / immunology
  • B-Lymphocytes / immunology*
  • Blood Proteins / immunology
  • Cell Adhesion Molecules
  • Cell Communication / immunology
  • Cell Differentiation
  • Cells, Cultured
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Immunity, Innate
  • Immunoglobulins / metabolism
  • Lymphocyte Activation
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mucoproteins / metabolism
  • Neutrophils / immunology
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Picrates / immunology
  • Plasma Cells / immunology*
  • Signal Transduction / immunology
  • Spleen / immunology*
  • Stromal Cells / immunology

Substances

  • Antibodies
  • Antigens, T-Independent
  • Blood Proteins
  • Cell Adhesion Molecules
  • Immunoglobulins
  • MADCAM1 protein, human
  • Mucoproteins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Picrates
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • picric acid