B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis.
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.
Clinical Immunology and Rheumatology, Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, The Netherlands.
Tineke
T
Cantaert
Johanna
J
Kolln
Trieneke
T
Timmer
Tineke C
TC
van der Pouw Kraan
Bernard
B
Vandooren
Rogier M
RM
Thurlings
Juan D
JD
Cañete
Anca I
AI
Catrina
Theo
T
Out
Cor L
CL
Verweij
Yiping
Y
Zhang
Paul P
PP
Tak
Dominique
D
Baeten
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D018925:Chemokines / Q000378:metabolism; D002828:Choristoma / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013585:Synovitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000378:metabolism
D001323:Autoantibodies; D053264:B-Cell Activating Factor; D018925:Chemokines; C108467:TNFRSF13B protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein