title: Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells.
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.
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Magri
authors.affiliation: Laboratory for Mucosal Immunity, RIKEN Center for Integrative Medical Sciences, RIKEN Yokohama, Tsurumi, Yokohama, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Miyajima
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bascones
authors.affiliation: Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Mortha
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Puga
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Linda
authors.initials: L
authors.lastname: Cassis
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Barra
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Comerma
authors.affiliation: Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Chudnovskiy
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gentile
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Llige
authors.affiliation: Immunology Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cols
authors.affiliation: Department of Pathology, Hospital del Mar, Universitat Autònoma de Barcelona and Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Serrano
authors.affiliation: Immunology Service, Hospital Clínic of Barcelona, Barcelona, Spain.
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Aróstegui
authors.affiliation: Immunology Service, Hospital Clínic of Barcelona, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Juan
authors.affiliation: Immunology Service, Hospital Clínic of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Yagüe
authors.affiliation: Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Immunology Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.affiliation: Laboratory for Mucosal Immunity, RIKEN Center for Integrative Medical Sciences, RIKEN Yokohama, Tsurumi, Yokohama, Japan.
authors.forename: Sidonia
authors.initials: S
authors.lastname: Fagarasan
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.|Immunology Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Catalan Institute for Research and Advanced Studies (ICREA), Barcelona Biomedical Research Park, Barcelona, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerutti
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D000955:Antigens, T-Independent / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology; D015815:Cell Adhesion Molecules; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007136:Immunoglobulins / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009088:Mucoproteins / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D010851:Picrates / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology
chemical_list: D000906:Antibodies; D000955:Antigens, T-Independent; D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010851:Picrates; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C005858:picric acid