دورية أكاديمية

Immunoglobulin VH-gene usage of autoantibodies in mercuric chloride-induced membranous glomerulopathy in the rat.

التفاصيل البيبلوغرافية
العنوان: Immunoglobulin VH-gene usage of autoantibodies in mercuric chloride-induced membranous glomerulopathy in the rat.
المؤلفون: Dammers PM; Department of Cell Biology, Immunology Section, University of Groningen, the Netherlands. p.m.dammers@med.rug.nl, Bun JC, Bellon B, Kroese FG, Aten J, Bos NA
المصدر: Immunology [Immunology] 2001 Jun; Vol. 103 (2), pp. 199-209.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 0374672 Publication Model: Print Cited Medium: Print ISSN: 0019-2805 (Print) Linking ISSN: 00192805 NLM ISO Abbreviation: Immunology Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford : Blackwell Scientific Publications
مواضيع طبية MeSH: Autoantibodies/*biosynthesis , Autoimmune Diseases/*immunology , Genes, Immunoglobulin/*immunology , Glomerulonephritis, Membranous/*immunology, Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/immunology ; Autoimmune Diseases/chemically induced ; Autoimmune Diseases/genetics ; Autoimmunity ; Base Sequence ; Complementarity Determining Regions/genetics ; DNA, Complementary/genetics ; Genes, Immunoglobulin/genetics ; Glomerulonephritis, Membranous/chemically induced ; Glomerulonephritis, Membranous/genetics ; Immunoglobulin Class Switching ; Laminin/immunology ; Mercuric Chloride ; Molecular Sequence Data ; Rats ; Rats, Inbred BN
مستخلص: Brown-Norway (BN) and Dorus Zadel Black (DZB) rats develop a T-cell-dependent membranous glomerulopathy (MGP) with high proteinuria and antiglomerular basement membrane (GBM) autoreactive antibodies (Abs), upon exposure to mercuric chloride (HgCl2). Laminin is an important autoantigenic target of the anti-GBM Abs, absorbing approximately 30% of the anti-GBM reactivity. Although many anti-GBM Abs have undergone isotype switching, it is currently unclear whether affinity maturation occurs during the HgCl2-induced autoimmune response. To address this question we analysed the rearranged immunoglobulin heavy chain variable-region genes (VHDJH regions) of 15 mAbs that were previously obtained from HgCl2-treated rats. Seven of these mAbs exhibit reactivity towards laminin. Our study showed that the VH-gene usage of antilaminin mAbs is largely restricted to the PC7183 VH-gene family (six out of seven). In addition, we demonstrated that at least three out of six laminin reactive and five out of six non-laminin-binding mAbs are encoded by germline VH genes (a total of eight out of 12 mAbs). Of the eight mAbs that are encoded by germline VH genes, seven are of a non-immunoglobulin M (IgM) isotype, indicating that isotype switching has occurred in these mAbs in the absence of somatic mutations. The mutations observed in the VH genes of the four remaining mAbs do not provide strong evidence for antigenic selection. The data support the notion that B cells in this model of MGP are not subjected to affinity maturation and probably result from polyclonal B-cell activation.
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المشرفين على المادة: 0 (Antibodies, Monoclonal)
0 (Autoantibodies)
0 (Complementarity Determining Regions)
0 (DNA, Complementary)
0 (Laminin)
53GH7MZT1R (Mercuric Chloride)
تواريخ الأحداث: Date Created: 20010620 Date Completed: 20010719 Latest Revision: 20190513
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC1783231
DOI: 10.1046/j.1365-2567.2001.01231.x
PMID: 11412307
قاعدة البيانات: MEDLINE
الوصف
تدمد:0019-2805
DOI:10.1046/j.1365-2567.2001.01231.x