Invariant natural killer T (NKT) cells serve as early rapid responders in the innate immune response to self-derived autoantigens and pathogen-derived danger signals and antigens. NKT cells can serve both as helpers for effector B cells and negatively regulate autoreactive B cells. Specifically, NKT cells drive B cell proliferation, class switch, and antibody production to induce primary antigen-specific immune responses. On the other hand, inflammasome-mediated activation drives accumulation of neutrophils, which license NKT cells to negatively regulate autoreactive B cells via Fas ligand (FasL). This positions NKT cells at an apex to support or inhibit B cell responses in inflammation. However, it is unknown which effector mechanism dominates in the face of cognate glycolipid activation during chronic inflammation, as might result from glycolipid vaccination or infection during chronic autoimmune disease. We stimulated NKT cells by cognate glycolipid antigen α-galactosylceramide (αGalCer) and measured B cell activation during interleukin 18 (IL-18)-induced chronic inflammation. Moreover, glycolipid-activated NKT cells increased the serum concentration of autoantibodies, frequency of germinal center (GC) B cells, and antigen-specific plasma cells induced during chronic IL-18-mediated inflammation, as compared with IL-18 alone. Further, activation of NKT cells via cognate glycolipid during IL-18-mediated inflammation overrides the licensing function of neutrophils, instead inducing NKT follicular helper (NKTfh) cells that in turn promote autoimmunity. Thus, our data demonstrate that glycolipids which engage NKT cells support antigen-specific B cell help during inflammasome-mediated inflammation.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183147PMC
http://dx.doi.org/10.1073/pnas.1920463117DOI Listing

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