B cells are important as antigen presenting cells for induction of MHC-restricted arthritis in transgenic mice.
Rheumatoid arthritis and its animal model, collagen-induced arthritis, are known as a T and B cell dependent disease. To analyze the role of B cells in arthritis, we generated B cell deficient (microMT) mice carrying HLA-DQ8 as transgene, Abetao.DQ8.micromt mice. HLA-DQ8 transgenic mice (Abetao.DQ8) are susceptible to collagen induced arthritis, an animal model for inflammatory arthritis. Deletion of IgM gene led to the absence of B cells while T cells were comparable to Abetao.DQ8 mice. Arthritis and autoantibodies was completely abrogated in B cell deficient DQ8 mice. T cell response and proinflammatory cytokine production in response to type II collagen and its derived peptides in vitro was significantly decreased despite an increased number of Mac-1 positive cells in DQ8.micromt mice compared to DQ8 mice suggesting B cells could be important for antigen presentation as well. In vitro substitution of B cells from wild type mice restored the response in DQ8.micromt mice. B cells could also present CII-derived peptides to antigen-specific DQ8-restricted hybridomas reinforcing the role of B cells in presentation of antigens to T cells. The data suggest that B cells can be involved in pathogenesis of arthritis by producing autoantibodies and antigen presentation.
Taneja
Veena
V
Department of Immunology, Mayo Clinic, 200 Ist Street SW, Rochester, MN 55905, USA. taneja.veena@mayo.edu
Krco
Christopher J
CJ
Behrens
Marshall D
MD
Luthra
Harvinder S
HS
Griffiths
Marie M
MM
David
Chella S
CS
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D017951:Antigen Presentation; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D005802:Genes, MHC Class II / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D019076:Transgenes
D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen