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.
Cantaert
Tineke
T
Clinical Immunology and Rheumatology, Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, The Netherlands.
Kolln
Johanna
J
Timmer
Trieneke
T
van der Pouw Kraan
Tineke C
TC
Vandooren
Bernard
B
Thurlings
Rogier M
RM
Cañete
Juan D
JD
Catrina
Anca I
AI
Out
Theo
T
Verweij
Cor L
CL
Zhang
Yiping
Y
Tak
Paul P
PP
Baeten
Dominique
D
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