title: Tolerogenic immunoreceptor ILT3/LILRB4 paradoxically marks pathogenic auto-antibody-producing plasmablasts and plasma cells in non-treated SLE.
abstract: Plasmablasts and plasma cells (PBs and PCs) producing pathogenic auto-antibodies in patients with systemic autoimmune diseases could be a better target for specific therapies for the disease than general immunosuppression or pan- or activated B-cell targeting. Our previous study indicated that leukocyte immunoglobulin-like receptor (LILR) B4 (B4, also known as ILT3/LIR-5/CD85k), a tolerogenic receptor in antigen-presenting cells, is ectopically expressed on the PB/PC surface in healthy individuals. Here, we show that the enlarged population size of PBs/PCs with augmented B4 expression is characteristic in non-treated systemic lupus erythematosus (SLE). Paradoxically, the transcription frequency of the anti-double-strand DNA immunoglobulin-coding VHsequence in the B4+population of non-treated SLE was significantly higher than that in B4-cells. B4+and B4-PBs/PCs were suggested to be developmentally equivalent based on the simultaneous generation of these populations upon activation of memory B cells in vitro B4 expression was found to be induced efficiently by IL-2, while IFN-α effectively induced B4+PBs/PCs in vitro Utilizing the elevated B4 will support opening a new avenue for identifying the mechanism for generation of, and additional molecular markers for, pathogenic cells.
authors.affiliation: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Sendai 980-8575, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Inui
authors.affiliation: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Sendai 980-8575, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sugahara-Tobinai
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Sendai 980-8575, Japan.
authors.forename: Ari
authors.initials: A
authors.lastname: Itoh-Nakadai
authors.affiliation: Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Fukuyama
authors.affiliation: Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.|Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.affiliation: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Sendai 980-8575, Japan toshiyuki.takai.b8@tohoku.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D011971:Receptors, Immunologic; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C107907:LILRB4 protein, human; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic
keywords: B-cell development; autoimmunity; plasma cell; tolerance