Document Detail

Expression of recombination-activating genes and terminal deoxynucleotidyl transferase and secondary rearrangement of immunoglobulin kappa light chains in rheumatoid arthritis synovial tissue.
MedLine Citation:
PMID:  11665968     Owner:  NLM     Status:  MEDLINE    
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. CONCLUSION: 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.
Z Zhang; X Wu; B H Limbaugh; S L Bridges
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  44     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-22     Completed Date:  2001-12-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2275-84     Citation Subset:  AIM; IM    
The University of Alabama at Birmingham, and Birmingham VA Medical Center, USA.
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MeSH Terms
Aged, 80 and over
Arthritis, Rheumatoid / genetics*,  immunology,  pathology
DNA Nucleotidylexotransferase / genetics*
Gene Expression Regulation
Gene Rearrangement
Genes, Immunoglobulin
Immunoglobulin kappa-Chains / genetics*
Middle Aged
Polymerase Chain Reaction
Recombination, Genetic
Synovial Membrane / immunology,  pathology
Grant Support
Reg. No./Substance:
0/Immunoglobulin kappa-Chains; EC Nucleotidylexotransferase

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