1.CD1d(hi)CD5⁺ B cells differentiate into antibody-secreting cells under the stimulation with calreticulin fragment.
Tengteng ZHANG ; Yun XIA ; Lijuan ZHANG ; Wanrong BAO ; Chao HONG ; Xiao-Ming GAO
Protein & Cell 2013;4(11):872-881
Calreticulin (CRT) is a multifunctional molecule in both intracellular and extracellular environment. We have previously found that a recombinant CRT fragment (rCRT/39-272) could modulate T cell-mediated immunity in mice via activation and expansion of CD1d(hi)CD5⁺ B cells as well as induction of CRT-specific regulatory antibodies. Antibody secreting cells (ASCs) are terminally differentiated B cells responsible for producing antibodies to participate in positive immune response as well as immune regulation. In this study, we demonstrate that rCRT/39-272 differentiates murine CD1d(hi)CD5⁺ B cells into ASCs marked by increased expression of plasma cell-associated transcription factors and production of polyreactive antibodies against DNA and CRT in vitro. Intraperitoneal administration of rCRT/39-272 augmented differentiation of CD1d(hi)CD5⁺ B cells into ASCs in naïve mice or mice with experimental autoimmune encephalomyelitis. Thus, we propose that ASC differentiation and subsequent antibody production of CD1d(hi)CD5⁺ B cells are key steps in CRT-mediated immunoregulation on inflammatory T cell responses.
Animals
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Antigens, CD1d
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metabolism
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Autoantibodies
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biosynthesis
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B-Lymphocytes
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cytology
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drug effects
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immunology
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metabolism
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CD5 Antigens
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metabolism
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Calreticulin
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chemistry
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Cell Differentiation
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drug effects
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Encephalomyelitis, Autoimmune, Experimental
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immunology
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Humans
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Mice
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Peptide Fragments
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chemistry
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pharmacology
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Solubility
2.The requirement of natural killer T-cells in tolerogenic APCs-mediated suppression of collagen-induced arthritis.
Sundo JUNG ; Yoon Kyung PARK ; Jung Hoon SHIN ; Hyunji LEE ; Soo Young KIM ; Gap Ryol LEE ; Se Ho PARK
Experimental & Molecular Medicine 2010;42(8):547-554
TGF-beta-induced tolerogenic-antigen presenting cells (Tol-APCs) could induce suppression of autoimmune diseases such as collagen-induced arthritis (CIA) and allergic asthma. In contrast, many studies have shown that NKT cells are involved in the pathogenesis of Th1-mediated autoimmune joint inflammation and Th2-mediated allergic pulmonary inflammation. In this study, we investigated the effect of CD1d-restricted NKT cells in the Tol-APCs-mediated suppression of autoimmune disease using a murine CIA model. When CIA-induced mice were treated with Tol-APCs obtained from CD1d+/- or CD1d-/- mice, unlike CD1d+/- APCs, CD1d-/- Tol-APCs failed to suppress CIA. More specifically, CD1d-/- Tol-APCs failed to suppress the production of inflammatory cytokines and the induction of Th2 responses by antigen-specific CD4 T cells both in vitro and in vivo. Our results demonstrate that the presence of CD1d-restricted NKT cells is critical for the induction of Tol-APCs-mediated suppression of CIA.
Animals
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Antibodies/blood
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Antibody Formation/immunology
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Antibody Specificity/immunology
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Antigen-Presenting Cells/*immunology
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Antigens, CD1d/immunology
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Arthritis, Experimental/blood/*immunology/*prevention & control
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Collagen Type II/immunology
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Cytokines/blood
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Immune Tolerance/*immunology
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Inflammation Mediators/blood
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Mice
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Natural Killer T-Cells/*immunology
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Th1 Cells/immunology