Diversity, cellular origin and autoreactivity of antibody-secreting cell expansions in acute Systemic Lupus Erythematosus
Autor: | Ramit Mehr, Jaime Darce, Travis Ichikawa, Iñaki Sanz, Alexander F. Rosenberg, Christopher M. Tipton, F. Eun-Hyung Lee, Christopher F. Fucile, Chungwen Wei, Ron J. Feldman, Scott A. Jenks, Wan Cheung Cheung, Sandra M Schieferl, Asiya Seema Chida, Ivan V. Gregoretti, Jennifer Hom |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Proteomics
Proteome Immunology Population Naive B cell Molecular Sequence Data Immunoglobulin Variable Region Biology Deep sequencing Article Pathogenesis Tandem Mass Spectrometry medicine Tetanus Toxoid Immunology and Allergy Humans Lupus Erythematosus Systemic Amino Acid Sequence education Antibody-Producing Cells Autoantibodies Cell Proliferation education.field_of_study B-Lymphocytes Lupus erythematosus Base Sequence Sequence Homology Amino Acid Autoantibody Germinal center medicine.disease Flow Cytometry Clone Cells Influenza Vaccines Immunoglobulin G Acute Disease Single-Cell Analysis Immunoglobulin Heavy Chains Anti-SSA/Ro autoantibodies Antibody Diversity |
Zdroj: | Nature immunology |
ISSN: | 1529-2916 1529-2908 |
Popis: | Acute systemic lupus erythematosus (SLE) courses with surges of antibody-secreting cells (ASCs) whose origin, diversity and contribution to serum autoantibodies remain unknown. Here, deep sequencing, proteomic profiling of autoantibodies and single-cell analysis demonstrated highly diversified ASCs punctuated by clones expressing the variable heavy-chain region VH4-34 that produced dominant serum autoantibodies. A fraction of ASC clones contained autoantibodies without mutation, a finding consistent with differentiation outside the germinal centers. A substantial ASC segment was derived from a distinct subset of newly activated naive cells of considerable clonality that persisted in the circulation for several months. Thus, selection of SLE autoreactivities occurred during polyclonal activation, with prolonged recruitment of recently activated naive B cells. Our findings shed light on the pathogenesis of SLE, help explain the benefit of agents that target B cells and should facilitate the design of future therapies. |
Databáze: | OpenAIRE |
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