title: Expression of recombination-activating genes and terminal deoxynucleotidyl transferase and secondary rearrangement of immunoglobulin kappa light chains in rheumatoid arthritis synovial tissue.
abstract: OBJECTIVE
  Lymphocytic infiltrates in rheumatoid arthritis (RA) synovium often resemble lymphoid follicles and contain clonally related Ig transcripts, suggesting in situ antigen-dependent B cell selection. Recent reports have shown expression of recombination-activating genes (RAGs) and concurrent secondary rearrangement of Ig genes in normal peripheral lymphoid organs (receptor revision). We sought to determine if RAG-mediated receptor revision of Ig kappa light chains occurs in B cells within the RA synovium. Because we previously reported enhanced N-region addition at V(L)-J(L) joins in clonally expanded light-chain transcripts from RA synovium, we also sought expression of terminal deoxynucleotidyl transferase (TdT), which is normally expressed only in B cell precursors or immature B cells.
  
  
  METHODS
  Reverse transcription-polymerase chain reaction (PCR) was used to detect RAG and TdT transcripts from unselected and B cell-enriched synovial and peripheral blood mononuclear cells obtained from 12 RA patients. Activity of RAG protein was sought using ligation-mediated PCR to detect recombination intermediates, and immunohistochemistry was performed to identify RAG+ cells within synovia.
  
  
  RESULTS
  We found evidence of RAG-mediated secondary Ig kappa light chain rearrangements in about one-third of RA synovia. TdT expression was found in several samples, but did not correlate with RAG expression.
  
  
  CONCLUSIONS
  RAG-mediated secondary Ig rearrangements of kappa light chains may contribute to the local production of antibodies to autoantigens (e.g., rheumatoid factor) or exogenous antigens, or it may represent a failed attempt at immune tolerance. TdT expression suggests the presence of immature B cells in RA synovia. These findings have important implications for the local generation of antibodies in RA and other chronic inflammatory diseases.
authors.affiliation: The University of Alabama at Birmingham, and Birmingham VA Medical Center, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: B H
authors.initials: BH
authors.lastname: Limbaugh
authors.forename: S L
authors.initials: SL
authors.lastname: Bridges
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004253:DNA Nucleotidylexotransferase / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology
chemical_list: D007145:Immunoglobulin kappa-Chains; D004253:DNA Nucleotidylexotransferase