title: Incomplete B cell tolerance to cartilage oligomeric matrix protein in mice.
abstract: OBJECTIVE
  Cartilage oligomeric matrix protein (COMP) is a major noncollagenous component of cartilage and is used as a biomarker in rheumatoid arthritis and experimental arthritis. Injection of COMP leads to severe inflammatory joint disease, and antibodies play a critical role in mediating arthritis. The arthritogenicity of COMP might be due to the lack of self tolerance. This study was undertaken to determine the status of COMP-specific B cell tolerance using COMP-deficient mice.
  
  
  METHODS
  Arthritis development and antibody responses were compared between COMP-sufficient and COMP-deficient littermates after immunization with rat COMP. Serum anti-COMP antibody levels were measured using a panel of recombinant mouse COMP proteins, and antibody-secreting cells were enumerated by enzyme-linked immunospot assays. A novel sandwich enzyme-linked immunosorbent assay was developed to assess COMP molecules in serum.
  
  
  RESULTS
  COMP-sufficient mice, but not COMP-deficient mice, developed severe arthritis following immunization with rat COMP. However, anti-COMP antibody titers to native COMP and recombinant protein domains covering the entire mouse COMP sequence, except the less immunodominant type 3 repeat domains, were decreased in COMP-sufficient mice compared to COMP-deficient mice. In addition, COMP-sufficient mice had fewer B cells secreting COMP-reactive antibodies. Detectable levels of full-length COMP in arthritic COMP-sufficient B10.Q NCF-1(*/*) and healthy mice suggested systemic availability of COMP to the immune system.
  
  
  CONCLUSIONS
  The lack of arthritis, together with high levels of COMP-specific antibodies, in COMP-deficient mice indicates that susceptibility to arthritis is COMP specific and that endogenous expression of COMP in wild-type mice tolerizes B cells in vivo.
authors.affiliation: Central China Normal University, Wuhan, China; Karolinska Institute, Stockholm, Sweden.
authors.forename: Hui
authors.initials: H
authors.lastname: Geng
authors.forename: Kutty Selva
authors.initials: KS
authors.lastname: Nandakumar
authors.forename: Li
authors.initials: L
authors.lastname: Xiong
authors.forename: Rui
authors.initials: R
authors.lastname: Jie
authors.forename: Jiahui
authors.initials: J
authors.lastname: Dong
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001323:Autoantibodies; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002356:Cartilage / Q000276:immunology / Q000378:metabolism*; D064236:Cartilage Oligomeric Matrix Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D007108:Immune Tolerance / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001323:Autoantibodies; D064236:Cartilage Oligomeric Matrix Protein