title: Local antigen-driven oligoclonal expansion of B cells in the liver portal areas of patients with primary biliary cirrhosis.
abstract: OBJECTIVE
  The antigen-driven clonal proliferation of B cells within target tissue has been reported in some autoimmune diseases. The purpose of this study was to examine the clonal characteristics of B cells in the liver portal area of primary biliary cirrhosis (PBC).
  
  
  METHODS
  The liver portal area was microdissected from liver biopsy sections from two PBC patients. Genomic DNA was extracted and rearranged immunoglobulin heavy chain variable region (VH) genes were amplified and sequence analyzed.
  
  
  RESULTS
  Sixteen VH sequences from portal area 1A of patient 1 had three different rearrangements. Nineteen VH sequences from portal area 1B of this patient had three different rearrangements. In three sequences from the portal area 1B, a stepwise accumulation of somatic mutations was observed. Between the sequences from the two portal areas, no common VH sequence was observed. In patient 2, 15 VH sequences from portal area 2A had three different rearrangements. Fourteen VH sequences from portal area 2B had two different rearrangements. One rearrangement was present both in the portal area 2A and portal area 2B.
  
  
  CONCLUSIONS
  The oligoclonal B cell proliferation and stepwise accumulation of somatic mutations suggested that an antigen-driven B cell response had occurred in the portal area of PBC.
authors.affiliation: Division of Clinical Immunology, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Beppu, Oita, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shiokawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Haraoka
authors.forename: Kyoko
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Junji
authors.initials: J
authors.lastname: Nishimura
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D002455:Cell Division / Q000276:immunology; D000939:Epitopes; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008099:Liver / Q000276:immunology* / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000473:pathology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D016133:Polymerase Chain Reaction
chemical_list: D000939:Epitopes; D007135:Immunoglobulin Variable Region