title: Early differentiated CD138(high) MHCII+ IgG+ plasma cells express CXCR3 and localize into inflamed kidneys of lupus mice.
abstract: Humoral responses are central to the development of chronic autoimmune diseases such as systemic lupus erythematosus. Indeed, autoantibody deposition is responsible for tissue damage, the kidneys being one of the main target organs. As the source of pathogenic antibodies, plasma cells are therefore critical players in this harmful scenario, both at systemic and local levels. The aim of the present study was to analyze plasma cells in NZB/W lupus mice and to get a better understanding of the mechanisms underlying their involvement in the renal inflammation process. Using various techniques (i.e. flow cytometry, quantitative PCR, ELISpot), we identified and extensively characterized three plasma cell intermediates, according to their B220/CD138/MHCII expression levels. Each of these cell subsets displays specific proliferation and antibody secretion capacities. Moreover, we evidenced that the inflammation-related CXCR3 chemokine receptor is uniquely expressed by CD138(high)MHCII(+) plasma cells, which encompass both short- and long-lived cells and mostly produce IgG (auto)antibodies. Expression of CXCR3 allows efficient chemotactic responsiveness of these cells to cognate chemokines, which production is up-regulated in the kidneys of diseased NZB/W mice. Finally, using fluorescence and electron microscopy, we demonstrated the presence of CD138(+)CXCR3(+)IgG(+) cells in inflammatory areas in the kidneys, where they are very likely involved in the injury process. Thus, early differentiated CD138(high)MHCII(+) rather than terminally differentiated CD138(high)MHCII(low) plasma cells may be involved in the renal inflammatory injury in lupus, due to CXCR3 expression and IgG secretion.
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunopathologie et Chimie Thérapeutique/Laboratory of Excellence Medalis, Strasbourg, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lacotte
authors.forename: Marion
authors.initials: M
authors.lastname: Decossas
authors.forename: Carole
authors.initials: C
authors.lastname: Le Coz
authors.forename: Susana
authors.initials: S
authors.lastname: Brun
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
authors.forename: Hélène
authors.initials: H
authors.lastname: Dumortier
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010950:Plasma Cells / Q000378:metabolism* / Q000648:ultrastructure; D054367:Receptors, CXCR3 / Q000096:biosynthesis*; D053668:Syndecan-1 / Q000096:biosynthesis*
chemical_list: D001323:Autoantibodies; C515188:Cxcr3 protein, mouse; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D054367:Receptors, CXCR3; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D017493:Leukocyte Common Antigens