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

Nature Immunology

(2014)

doi:10.1038/ni.2830

Received: 09 December 2013
Accepted: 16 January 2014
Published online: 23 February 2014

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.