Volume 1 Supplement 1

Fourth International Synovitis Workshop

Open Access

Expression of RAG1, RAG2, and TdT in Rheumatoid Arthritis Synovia: Evidence for Receptor Revision of Immunoglobulin Light Chains

  • S Louis Bridges Jr1 and
  • Zhixin Zhang1
Arthritis Research & Therapy19991(Suppl 1):S10

DOI: 10.1186/ar24

Published: 15 November 1999

Full text

Some rheumatoid arthritis (RA) synovia contain structures similar to germinal centers (GC), the site of affinity maturation of B lymphocytes [1,2]. Previous analyses of immunoglobulin (Ig) kappa and lambda light chains expressed in RA synovia showed clonally related sequences with frequent N region addition and unusually long CDR3s [3,4]. The presence of clonally related Ig heavy chain sequences in GC-like structures from RA synovia suggests in situ antigen-dependent B cell maturation. RAG1 and 2, enzymes that mediate V(D)J recombination during B cell development, are expressed in a subset of GC B cells in normal peripheral lymphoid organs [5,6]. RAG expression allows secondary Ig rearrangements, which salvages B cells with undesirable specificities or low antigen affinity (receptor revision). We sought to determine whether RAG and TdT (the enzyme responsible for N region addition) are expressed in RA synovia and whether secondary Ig rearrangements occur. Using nested RT-PCR, we detected RAG1, RAG2, and TdT mRNA in 8, 9, and 6 of 12 synovial samples (11 RA, 1 JRA), respectively. RAG1 was expressed in B cells (5/8 samples) and T cells (4/8). RAG2 was expressed in B cells (4/8) more often than in T cells (1/8). TdT was expressed in B cells only (2/8). Immunohistochemical staining indicated that RAG proteins were distributed in lymphoid aggregates. In some synovia, secondary rearrangement products (ds-DNA breaks at recombination signal sequences in the Jkappa region) were detected by ligation-mediated PCR. We speculate that receptor revision in nonlymphoid tissues such as RA synovia may generate autoreactive antibodies, which has important implications for chronic inflammatory diseases.

Authors’ Affiliations

University of Alabama at Birmingham and Birmingham VA Medical Center


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