Recruitment of fibrillarin to the antigen processing machinery by mercury: implications for processing of a nucleolar autoantigen

Journal/Book: Z Rheumatol 1999; 58 Suppl. 1: I/27 (FE 22). 1999;

Abstract: 1Junior Research Group Molecular Cell Biology Medical Institute of Environmental Hygiene Heinrich-Heine-University Duesseldorf; 2Dept. Molecular Biology Institute for Molecular Biotechnology Jena Administration of mercury ions to mice elicits an anti-nucleolar autoantibody (ANoA) response that targets fibrillarin a 34 kD protein component of many small nucleolar ribonucleoprotein (snoRNP) particles. Autoantibodies thus induced react with a conserved epitope of fibrillarin similar to the anti-fibrillarin response diagnostic of a subset of human scleroderma patients. In order to investigate cell biological events underlying this B-cell response we developed a cell culture system to monitor subcellular fibrillarin distribution: After treatment with mercuric chloride (HgC12) we observe in interphase cells a time and cell cycle dependent redistribution of fibrillarin from the nucleolus into the nucleoplasm. Nucleoplasmic fibrillarin co-localizes with the 20S proteasome a self-compartmentalizing protease delivering immunocompetent peptides to the antigen processing machinery via MHC class I molecules. We think that mercury ions penetrate the cell/nucleus alter the structure and change the molecular context (=subcellular redistribution) of fibrillarin thus permitting the efficient processing/presentation of previously cryptic determinants and breaking tolerance of the immune system to self determinants. le

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