title: NKT Cell Hyporesponsiveness Leads to Unrestrained Accumulation of Marginal Zone B Cells in Hypercholesterolemic Apolipoprotein E-Deficient Mice.
abstract: Recently, the role of B cells in atherosclerosis has gained more attention but studies have mainly focused on B1 and follicular B cell subsets. Therefore, the contribution of marginal zone (MZ) B cells in experimental atherosclerosis remains elusive. In the current study, we examined the MZ B cell compartment in atherosclerotic apoE-deficient (apoE-/-) mice and found that hypercholesterolemia in these mice was associated with an increased number and percentage of MZ B cells. This aberrant accumulation of MZ B cells was not associated with alterations in their development or increased proliferation but was due to decreased apoptotic cell death. This decrease in MZ B cell death in apoE-/-mice was associated with the reduced capacity of invariant NKT (iNKT) cells to produce IFN-γ and IL-4 after activation. Lowering cholesterol plasma levels with ezetimibe in apoE-/-mice reversed iNKT function and MZ B cell accumulation. To elucidate the mechanism whereby iNKT cells control MZ B cell accumulation in apoE-/-mice, we performed an adoptive transfer of iNKT cells and found that only wild-type iNKT cells but not IFN-γ-/-iNKT cells reversed MZ B cell accumulation in apoE-/-recipient mice. Our findings reveal that lipid changes associated with atherosclerotic disease induce decreased production of IFN-γ by iNKT, which in turn leads to aberrant accumulation of MZ B cells. This study further extends the importance of iNKT cells in regulating MZ B cell compartment.
authors: Department of Microbiology, Immunology Programme, Life Science Institute, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.
authors: Serena Ying
authors: SY
authors: Soh
authors: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, 59800 Lille, France.|Université Lille Nord de France, 59019 Lille Cedex, France.|Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8204, 59019 Lille Cedex, France.|INSERM, U1019, 59019 Lille Cedex, France; and.
authors: Christelle
authors: 0000-0002-8373-3992
authors: C
authors: Faveeuw
authors: Department of Microbiology, Immunology Programme, Life Science Institute, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.
authors: Chung Hwee
authors: CH
authors: Thiam
authors: Department of Microbiology, Immunology Programme, Life Science Institute, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.|Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore 138 648.
authors: Lawrence Han Boon
authors: 0000-0002-0020-5917
authors: LH
authors: Khoo
authors: Department of Microbiology, Immunology Programme, Life Science Institute, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.
authors: Kim Pin
authors: KP
authors: Yeo
authors: Department of Microbiology, Immunology Programme, Life Science Institute, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.
authors: Sheau Yng
authors: 0000-0002-5627-5017
authors: SY
authors: Lim
authors: Department of Microbiology, Immunology Programme, Life Science Institute, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.
authors: Hwee Ying
authors: HY
authors: Lim
authors: Department of Microbiology, Immunology Programme, Life Science Institute, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.
authors: Jun Xiang
authors: JX
authors: Ng
authors: Department of Microbiology, Immunology Programme, Life Science Institute, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore; micva@nus.edu.sg.|Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore 138 648.
authors: Veronique
authors: 0000-0002-2759-3497
authors: V
authors: Angeli
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000069438:Ezetimibe / Q000008:administration & dosage / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008221:Lymphoid Tissue / Q000033:anatomy & histology / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D015847:Interleukin-4; D007371:Interferon-gamma; D000069438:Ezetimibe