TY - JOUR
T1 - B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis
AU - Cantaert, Tineke
AU - Kolln, Johanna
AU - Timmer, Trieneke
AU - van der Pouw Kraan, Tineke C.
AU - Vandooren, Bernard
AU - Thurlings, Rogier M.
AU - Cañete, Juan D.
AU - Catrina, Anca I.
AU - Out, Theo
AU - Verweij, Cor L.
AU - Zhang, Yiping
AU - Tak, Paul P.
AU - Baeten, Dominique
PY - 2008
Y1 - 2008
N2 - B lymphocyte autoimmunity plays a crucial role in the pathogenesis of rheumatoid arthritis. The local production of autoantibodies and the presence of ectopic lymphoid neogenesis in the rheumatoid synovium suggest that these dedicated microenvironments resembling canonical lymphoid follicles may regulate the initiation and maturation of B cell autoimmunity. In this study, we assessed experimentally the relevance of ectopic lymphoid neogenesis for B cell autoimmunity by a detailed structural, molecular, and serological analysis of seropositive and seronegative human synovitis. We demonstrate that synovial lymphoid neogenesis is a reversible process associated with inflammation which is neither restricted to nor preferentially associated with autoantibody positive rheumatic conditions. Despite the abundant expression of key chemokines and cytokines required for full differentiation toward germinal center reactions, synovial lymphoid neogenesis in rheumatoid arthritis only occasionally progresses toward fully differentiated follicles. In agreement with that observation, we could not detect Ag-driven clonal expansion and affinity maturation of B lymphocytes. Furthermore, ectopic lymphoid neogenesis is not directly associated with local production of anti-citrullinated protein Abs and rheumatoid factor in the rheumatoid joint. Therefore, we conclude that synovial lymphoid neogenesis is not a major determinant of these rheumatoid arthritis-specific autoantibody responses
AB - B lymphocyte autoimmunity plays a crucial role in the pathogenesis of rheumatoid arthritis. The local production of autoantibodies and the presence of ectopic lymphoid neogenesis in the rheumatoid synovium suggest that these dedicated microenvironments resembling canonical lymphoid follicles may regulate the initiation and maturation of B cell autoimmunity. In this study, we assessed experimentally the relevance of ectopic lymphoid neogenesis for B cell autoimmunity by a detailed structural, molecular, and serological analysis of seropositive and seronegative human synovitis. We demonstrate that synovial lymphoid neogenesis is a reversible process associated with inflammation which is neither restricted to nor preferentially associated with autoantibody positive rheumatic conditions. Despite the abundant expression of key chemokines and cytokines required for full differentiation toward germinal center reactions, synovial lymphoid neogenesis in rheumatoid arthritis only occasionally progresses toward fully differentiated follicles. In agreement with that observation, we could not detect Ag-driven clonal expansion and affinity maturation of B lymphocytes. Furthermore, ectopic lymphoid neogenesis is not directly associated with local production of anti-citrullinated protein Abs and rheumatoid factor in the rheumatoid joint. Therefore, we conclude that synovial lymphoid neogenesis is not a major determinant of these rheumatoid arthritis-specific autoantibody responses
U2 - https://doi.org/10.4049/jimmunol.181.1.785
DO - https://doi.org/10.4049/jimmunol.181.1.785
M3 - Article
C2 - 18566445
SN - 0022-1767
VL - 181
SP - 785
EP - 794
JO - Journal of immunology (Baltimore, Md.
JF - Journal of immunology (Baltimore, Md.
IS - 1
ER -