title: B cells from rheumatoid arthritis patients show important alterations in the expression of CD86 and FcgammaRIIb, which are modulated by anti-tumor necrosis factor therapy.
abstract: BACKGROUND
  Several molecules help preserve peripheral B cell tolerance, but when altered, they may predispose to autoimmunity. This work studied the expression of the costimulatory molecule CD86 and the inhibitory receptor for IgG immune complexes FcgammaRIIb (CD32b), on B cells from rheumatoid arthritis (RA) patients, and the influence of anti-tumor necrosis factor (TNF) therapy.
  
  
  METHODS
  Peripheral B cells from 18 RA patients and 13 healthy donors were characterized using flow cytometry. Eleven patients who underwent a six-month adalimumab therapy were further assessed for phenotypic changes on their B cells.
  
  
  RESULTS
  RA patients exhibited a high percentage of naïve and memory B cells expressing CD86. In contrast, expression of FcgammaRIIb was significantly reduced on RA memory B cells and plasmablasts as compared to healthy donors, probably due to downregulation of this receptor when differentiating from naïve to memory cells. These alterations on FcgammaRIIb were associated with high levels of anti-citrullinated vimentin autoantibodies. In addition, treatment with adalimumab normalized the expression of CD86 on memory B cells and reduced the expression of FcgammaRIIb, mainly on naïve B cells.
  
  
  CONCLUSIONS
  Our findings show that peripheral B cells from RA patients have an altered expression of key molecules, such as CD86 and FcgammaRIIb. Because this latter receptor is required for feedback inhibition, a deficient expression might contribute to humoral autoimmune responses. Furthermore, these molecules are likely to be influenced by inflammatory factors, since they were modulated by TNF inhibition.
authors.affiliation: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile.
authors.forename: Diego
authors.initials: D
authors.lastname: Catalán
authors.forename: Octavio
authors.initials: O
authors.lastname: Aravena
authors.forename: Francisca
authors.initials: F
authors.lastname: Sabugo
authors.forename: Pamela
authors.initials: P
authors.lastname: Wurmann
authors.forename: Lilian
authors.initials: L
authors.lastname: Soto
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
authors.forename: Miguel
authors.initials: M
authors.lastname: Cuchacovich
authors.forename: Juan C
authors.initials: JC
authors.lastname: Aguillón
mesh_terms: D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism*; D005260:Female; D006801:Humans; D007596:Joints / Q000503:physiopathology; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism*; D012720:Severity of Illness Index; D014746:Vimentin / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001323:Autoantibodies; D051940:B7-2 Antigen; C497964:CD86 protein, human; C499173:FCGR2B protein, human; D010456:Peptides, Cyclic; D017452:Receptors, IgG; D014746:Vimentin; C487763:cyclic citrullinated peptide; D000068879:Adalimumab
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