title: Lipid-antigen presentation by CD1d(+) B cells is essential for the maintenance of invariant natural killer T cells.
abstract: B cells perform many immunological functions, including presenting lipid antigen to CD1d-restricted invariant natural killer T (iNKT) cells, known to contribute to maintaining tolerance in autoimmunity. Patients with systemic lupus erythematous (SLE) display dysregulated B cell responses and reduced peripheral iNKT cell frequencies. The significance of these defects and how they relate to SLE pathogenesis remain elusive. We report that B cells are essential for iNKT cell expansion and activation in healthy donors but fail to exert a similar effect in SLE patients. Defective B cell-mediated stimulation of iNKT cells in SLE patients was associated with altered CD1d recycling, a defect recapitulated in B cells from healthy donors after stimulation with interferon-α (IFN-α) and anti-immunoglobulin (Ig). iNKT cell number and function were restored in SLE patients responding to anti-CD20 treatment upon normalization of CD1d expression exclusively in repopulated immature B cells. We propose that healthy B cells are pivotal for iNKT cell homeostasis.
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, University College London, London WC1E 6JF, UK.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Bosma
authors.forename: Azza
authors.initials: A
authors.lastname: Abdel-Gadir
authors.forename: David A
authors.initials: DA
authors.lastname: Isenberg
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Jury
authors.forename: Claudia
authors.initials: C
authors.lastname: Mauri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D017951:Antigen Presentation; D055610:Antigens, CD1d / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008055:Lipids / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D000069283:Rituximab; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016207:Cytokines; D007166:Immunosuppressive Agents; D008055:Lipids; D000069283:Rituximab