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Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):E1399-407. doi: 10.1073/pnas.1107830108. Epub 2011 Dec 1.

The inflammatory cytokine IL-18 induces self-reactive innate antibody responses regulated by natural killer T cells.

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Translational Immunology Unit, Department of Medicine Solna, Karolinska Institute, 171 76 Stockholm, Sweden.


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.

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