TY - JOUR
T1 - The inflammatory cytokine IL-18 induces self-reactive innate antibody responses regulated by natural killer T cells
AU - Enoksson, Sara Lind
AU - Grasset, Emilie K.
AU - Hägglöf, Thomas
AU - Mattsson, Nina
AU - Kaiser, Ylva
AU - Gabrielsson, Susanne
AU - McGaha, Tracy L.
AU - Scheynius, Annika
AU - Karlsson, Mikael C.I.
PY - 2011/12/20
Y1 - 2011/12/20
N2 - 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.
AB - 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.
KW - Anti-DNA antibodies
KW - Biological sciences
KW - Immunology
KW - Marginal zone B cells
UR - http://www.scopus.com/inward/record.url?scp=84855490508&partnerID=8YFLogxK
U2 - 10.1073/pnas.1107830108
DO - 10.1073/pnas.1107830108
M3 - Article
C2 - 22135456
AN - SCOPUS:84855490508
SN - 0027-8424
VL - 108
SP - E1399-E1407
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 51
ER -