title: Despite ubiquitous autoantigen expression, arthritogenic autoantibody response initiates in the local lymph node.
abstract: K/BxN mice develop an inflammatory joint disease with many features characteristic of rheumatoid arthritis. In this model, the KRN transgenic T cells and nontransgenic B cells both recognize the glycolytic enzyme glucose-6-phosphate-isomerase (GPI) as an autoantigen. Here, we followed the anti-GPI B cell response that naturally arises in K/BxN mice. The anti-GPI B cell response was robust and arose at the same time as the development of serum anti-GPI autoantibody and joint inflammation. Surprisingly, although GPI was expressed systemically, the anti-GPI B cell response was focused to the lymph nodes (LN) draining the distal joints where arthritis was evident. In lymphotoxin-beta receptor-Ig-treated mice, which lack LNs, the development of arthritis was completely inhibited up to 5-6 weeks. At later times, some arthritis did develop, but at a significantly reduced level. Thus, in this spontaneous model of autoimmunity, the LNs draining the distal joints are essential for both the inhibition and amplification of the arthritogenic B cell response. These findings imply that the immune physiology of a joint is unique, resulting in a local immune response to a systemic autoantigen.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Mandik-Nayak
authors.forename: Brian T
authors.initials: BT
authors.lastname: Wipke
authors.forename: Fei F
authors.initials: FF
authors.lastname: Shih
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
authors.forename: Paul M
authors.initials: PM
authors.lastname: Allen
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D005956:Glucose-6-Phosphate Isomerase