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

Giuliana Magri, Michio Miyajima, Sabrina Bascones, Arthur Mortha, Irene Puga, Linda Cassis, Carolina M. Barra, Laura Comerma, Aleksey Chudnovskiy, Maurizio Gentile, David Llige, Montserrat Cols, Sergi Serrano, Juan Ignacio Aróstegui, Manel Juan, Jordi Yagüe, Miriam Merad, Sidonia Fagarasan, Andrea Cerutti

Research output: Contribution to journalArticleResearchpeer-review

174 Citations (Scopus)

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. © 2014 Nature America, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)354-364
JournalNature Immunology
Volume15
Issue number4
DOIs
Publication statusPublished - 1 Jan 2014

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