- Meeting abstract
Expression of RAG1, RAG2, and TdT in Rheumatoid Arthritis Synovia: Evidence for Receptor Revision of Immunoglobulin Light Chains
Arthritis Research & Therapy volume 1, Article number: S10 (1999)
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.
Randen I, Mellbye OJ, Førre O, Natvig JB: The identification of germinal centres and follicular dendritic networks in rheumatoid synovial tissue. Scand J Immunol. 1995, 41: 481-486.
Schröder AE, Greiner A, Seyfert C, Berek C: Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis. Proc Natl Acad Sci USA. 1996, 93: 221-225. 10.1073/pnas.93.1.221.
Bridges SL: Frequent N addition and clonal relatedness among immunoglobulin lambda light chains expressed in rheumatoid arthritis synovia and PBL, and the influence of Vlambda gene segment utilization on CDR3 length. Molecular Med. 1998, 4: 525-553.
Bridges SL, Lee SK, Johnson MJ, et al: Somatic mutation and CDR3 lengths of immunoglobulin kappa light chains expressed in patients with rheumatoid arthritis and normal individuals. J Clin Invest. 1995, 96: 831-841.
Papavasiliou F, Casellas R, Suh H, et al: V(D)J recombination in mature B cells: a mechanism for altering antibody responses. Science. 1997, 278: 298-301. 10.1126/science.278.5336.298.
Han S, Zheng B, Schatz DG, Spanopoulou E, Kelsoe G: Neoteny in lymphocytes: Rag1 and Rag2 expression in germinal center B cells. Science. 1996, 274: 2094-2097. 10.1126/science.274.5295.2094.
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Bridges Jr, S.L., Zhang, Z. Expression of RAG1, RAG2, and TdT in Rheumatoid Arthritis Synovia: Evidence for Receptor Revision of Immunoglobulin Light Chains. Arthritis Res Ther 1 (Suppl 1), S10 (1999). https://doi.org/10.1186/ar24