Nucleotide sequence analysis of natural and combinatorial anti-PDC-E2 antibodies in patients with primary biliary cirrhosis: Recapitulating immune selection with molecular biology Academic Article uri icon

Overview

MeSH Major

  • Autoantibodies
  • Liver Cirrhosis, Biliary
  • Pyruvate Dehydrogenase Complex

abstract

  • We have analyzed at the nucleotide level the variable region gene sequences of five human mAbs and five recombinant Fab fragments derived from the mesenteric lymph nodes of patients with primary biliary cirrhosis. Both mAbs and Fabs were monospecific for dihydrolipoamide acetyltransferase, the E2 subunit of the pyruvate dehydrogenase complex, which has been shown to be the major autoantigen of primary biliary cirrhosis. We found that although the mAbs, mainly of the IgM isotype, were encoded by a diverse array of VH and VL gene segments either as direct copies of germline genes or somatically mutated, the recombinant IgG Fabs expressed clonally related heavy chains displaying a high number of somatic mutations that very likely occurred in the context of Ag selection. Combinatorial pairing of clonally related heavy chains with highly homologous light chains suggests that the IgG anti-pyruvate dehydrogenase complex repertoire of primary biliary cirrhosis patients is the result of the clonal expansion of a restricted set of B cells.

publication date

  • March 1994

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 8133065

Additional Document Info

start page

  • 2577

end page

  • 85

volume

  • 152

number

  • 5