title: Aberrant presentation of self-lipids by autoimmune B cells depletes peripheral iNKT cells.
abstract: Invariant natural killer T (iNKT) cells provide cognate help via CD1d to lipid antigen-presenting B cells for antibody production, but whether B cells reciprocally regulate iNKT cells remains largely unexplored. Here, we found peripheral, but not thymic, iNKT cells to be numerically reduced in autoimmune mice lacking Fas specifically in B cells. The residual iNKT cells were antigenically overstimulated, had altered cytokine production, and manifested enhanced proliferation and apoptosis. B cell-specific ablation of CD1d ameliorated these iNKT defects, suggesting that inappropriate presentation of CD1d-restricted self-lipids by autoimmune B cell-depleted peripheral iNKT cells. CD1d(+) autoimmune B cells have reduced α-galactosidase A expression and, as revealed by lipidomic profiling, altered lipidome with aberrant accumulation of certain self-lipids and reduction of others. These findings unveil a critical link between autoimmunity, B cell lipidome, and the maintenance of peripheral iNKT cells and highlight an essential homeostatic function of B cells beyond antibody production.
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore; Microarray Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore. Electronic address: andy_tan@bti.a-star.edu.sg.
authors.forename: Andy Hee-Meng
authors.initials: AH
authors.lastname: Tan
authors.affiliation: Metabolomics Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore.
authors.forename: William Pooi-Kat
authors.initials: WP
authors.lastname: Chong
authors.affiliation: Microarray Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore.
authors.forename: Sze-Wai
authors.initials: SW
authors.lastname: Ng
authors.affiliation: Metabolomics Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore.
authors.forename: Nurhidayah
authors.initials: N
authors.lastname: Basri
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
authors.forename: Shengli
authors.initials: S
authors.lastname: Xu
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore. Electronic address: lam_kong_peng@bti.a-star.edu.sg.
authors.forename: Kong-Peng
authors.initials: KP
authors.lastname: Lam
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D008055:Lipids / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D008055:Lipids