title: NKG2D Promotes B1a Cell Development and Protection against Bacterial Infection.
abstract: NKG2D is a potent activating receptor that is expressed on cytotoxic immune cells such as CD8 T and NK cells, where it promotes cytotoxicity after binding stress ligands on infected or transformed cells. On NK cell precursors NKG2D modulates proliferation and maturation. Previously, we observed that NKG2D deficiency affects peripheral B cell numbers. In this study, we show that NKG2D regulates B1a cell development and function. We find that mice deficient for NKG2D have a strong reduction of B1a cell numbers. As a result, NKG2D-deficient mice produce significantly less Ag-specific IgM Abs upon immunization with T cell-independent Ags, and they are more susceptible to Gram-negative sepsis. Klrk1-/-B1a cells are also functionally impaired and they fail to provide protection against Francisella novicida upon adoptive transfer. Using mixed bone marrow chimeric mice, we show that the impact of NKG2D deficiency on B1a cell development is cell intrinsic. No changes in homeostatic turnover and homing of B cells were detectable, limiting the effects of NKG2D to modulation of the hematopoietic development of B1a cells. Using conditional ablation, we demonstrate that the effect of NKG2D on B1a cell development occurs at a developmental stage that precedes the common lymphoid progenitor. Our findings reveal an unexpected new role for NKG2D in the regulation of B1a cell development. The protective effects of this activating receptor therefore reach beyond that of cytotoxic cells, stimulating the immune system to fight bacterial infections by promoting development of innate-like B cells.
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Lenartić
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Vedrana
authors.initials: V
authors.lastname: Jelenčić
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.|Laboratory of Dendritic Cell Immunobiology, Immunology Department, Institute Pasteur, 75015 Paris, France.
authors.forename: Biljana
authors.identifier: 0000-0002-2297-1073
authors.initials: B
authors.lastname: Zafirova
authors.affiliation: Department of Microbiology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Mateja
authors.identifier: 0000-0002-7028-1245
authors.initials: M
authors.lastname: Ožanič
authors.affiliation: Department of Microbiology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marečić
authors.affiliation: Department of Medical Physics, University Hospital Rijeka, 51000 Rijeka, Croatia.
authors.forename: Slaven
authors.identifier: 0000-0001-7449-3889
authors.initials: S
authors.lastname: Jurković
authors.affiliation: Department of Biomedical Sciences, Institute of Pharmacology and Toxicology, University of Veterinary Medicine, 1210 Vienna, Austria; and.
authors.forename: Veronika
authors.identifier: 0000-0001-9363-0412
authors.initials: V
authors.lastname: Sexl
authors.affiliation: Department of Microbiology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Marina
authors.identifier: 0000-0003-4138-3581
authors.initials: M
authors.lastname: Šantić
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.|Department of Experimental Immunology, Academic Medical Center, 1105 Amsterdam, the Netherlands.
authors.forename: Felix M
authors.identifier: 0000-0002-1333-8882
authors.initials: FM
authors.lastname: Wensveen
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia; bojan.polic@medri.uniri.hr.
authors.forename: Bojan
authors.identifier: 0000-0003-3930-9630
authors.initials: B
authors.lastname: Polić
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D005603:Francisella / Q000276:immunology; D016905:Gram-Negative Bacterial Infections / Q000276:immunology* / Q000517:prevention & control; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000172:deficiency / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D007075:Immunoglobulin M; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K