[B lymphocyte differentiation in granulomatous tissues of the lung and the nasal mucosa in Wegener's granulomatosis: origin of anti-neutrophil cytoplasmic antibody formation?].

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  • Additional Information
    • Transliterated Title:
      B-Lymphozyten-Differenzierung in granulomatösen Geweben der Lunge und der Nasenschleimhäute beim Morbus Wegener: Ursprungsort der ANCA-Bildung?
    • Source:
      Publisher: Springer Country of Publication: Germany NLM ID: 0414162 Publication Model: Print Cited Medium: Print ISSN: 0340-1855 (Print) Linking ISSN: 03401855 NLM ISO Abbreviation: Z Rheumatol Subsets: MEDLINE
    • Publication Information:
      Publication: 2006- : Heidelberg : Springer
      Original Publication: Darmstadt, Steinkopff.
    • Subject Terms:
      Antibodies, Antineutrophil Cytoplasmic/*metabolism ; B-Lymphocytes/*immunology ; Granulomatosis with Polyangiitis/*immunology ; Lung/*immunology ; Lymphocyte Activation/*immunology ; Nasal Mucosa/*immunology; Aged ; Aged, 80 and over ; Autoantibodies/blood ; Autoantibodies/genetics ; Biopsy ; DNA Mutational Analysis ; Genes, Immunoglobulin Heavy Chain/genetics ; Granulomatosis with Polyangiitis/genetics ; Granulomatosis with Polyangiitis/pathology ; Humans ; Immunoenzyme Techniques ; Lung/pathology ; Middle Aged ; Myeloblastin/immunology ; Nasal Mucosa/pathology
    • Abstract:
      Wegener's granulomatosis (WG) starts with granulomatous inflammation of the respiratory tract before it converts into a potentially organ and life threatening systemic vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA). The site of formation of the highly specific ANCA directed against "Wegener's autoantigen" proteinase 3 (PR3) is still unknown. Previously, we have shown that follicle-like B lymphocytic infiltrates in the vicinity to PR3 expressing cells in WG-granulomata. We characterized the immunoglobulin-VH repertoire in lung and nasal granulomata (paraffin embedded) from four WG patients. A total of 115 individual VH genes were characterized and compared to 84 VH genes from the peripheral blood of a healthy donor. We found an increased frequency of mutations with a bias to amino acid exchanges within the antigen binding sites (CDR) 1 and 2 in WG tissue. A large number of mutations led to negatively charged amino acids and may increase affinity to the positively charged PR3. Furthermore, the occurrence of differently mutated members of one B cell clone indicates clonal expansion and intraclonal diversification by an antigen, e.g. PR3. Several WG tissue derived genes displayed similarities to published sequences from peripheral PR3 ANCA producing B cells. Thus, granulomata of the lower and upper respiratory tract contain follicle-like B cell clusters with a selected VH repertoire infiltrate in WG. WG granulomata could be the place of autoantigen presentation and formation of high-affinity ANCA within neoformed ectopic or tertiary lymphoid-like tissue areas.
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    • Accession Number:
      0 (Antibodies, Antineutrophil Cytoplasmic)
      0 (Autoantibodies)
      EC 3.4.21.76 (Myeloblastin)
    • Publication Date:
      Date Created: 20070523 Date Completed: 20080114 Latest Revision: 20181113
    • Publication Date:
      20240829
    • Accession Number:
      10.1007/s00393-007-0170-8
    • Accession Number:
      17516076