title: The inflammatory cytokine IL-18 induces self-reactive innate antibody responses regulated by natural killer T cells.
abstract: Inflammatory responses initiate rapid production of IL-1 family cytokines, including IL-18. This cytokine is produced at high levels in inflammatory diseases, including allergy and autoimmunity, and is known to induce IgE production in mice. Here we provide evidence that IL-18 is directly coupled to induction of self-reactive IgM and IgG antibody responses and recruitment of innate B2 B cells residing in the marginal zone of the spleen. Moreover, the data suggest that the B-cell activation occurs predominantly in splenic extrafollicular plasma cell foci and is regulated by natural killer T (NKT) cells that prevent formation of mature germinal centers. We also find evidence that NKT cells control this type of B-cell activation via cytotoxicity mediated by both the perforin and CD95/CD178 pathways. Thus, NKT cells regulate innate antibody responses initiated by an inflammatory stimulus, suggesting a general mechanism that regulates B-cell behavior in inflammation and autoreactivity.
authors.affiliation: Translational Immunology Unit, Department of Medicine Solna,  Karolinska Institute, 171 76 Stockholm,  Sweden.
authors.forename: Sara Lind
authors.initials: SL
authors.lastname: Enoksson
authors.forename: Emilie K
authors.initials: EK
authors.lastname: Grasset
authors.forename: Thomas
authors.initials: T
authors.lastname: Hägglöf
authors.forename: Nina
authors.initials: N
authors.lastname: Mattsson
authors.forename: Ylva
authors.initials: Y
authors.lastname: Kaiser
authors.forename: Susanne
authors.initials: S
authors.lastname: Gabrielsson
authors.forename: Tracy L
authors.initials: TL
authors.lastname: McGaha
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.forename: Mikael C I
authors.initials: MC
authors.lastname: Karlsson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D018941:Antigens, CD19 / Q000235:genetics; D002469:Cell Separation; D053222:Fas Ligand Protein / Q000096:biosynthesis; D005260:Female; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D020382:Interleukin-18 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D000906:Antibodies; D018941:Antigens, CD19; D053222:Fas Ligand Protein; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020382:Interleukin-18; D019014:fas Receptor