TY - JOUR
T1 - B cells are important as antigen presenting cells for induction of MHC-restricted arthritis in transgenic mice
AU - Taneja, Veena
AU - Krco, Christopher J.
AU - Behrens, Marshall D.
AU - Luthra, Harvinder S.
AU - Griffiths, Marie M.
AU - David, Chella S.
N1 - Funding Information:
Authors acknowledge Julie Hanson and Tad Trejo for maintaining transgenic mice and Michele Smart for screening the transgenic mice. Funding source: The study was supported by grants from National Arthritis Foundation Investigator Award to Veena Taneja and NIH AR 30752. The HLA Class II transgenic mice were produced with the support from NIH grant AI 14764.
PY - 2007/4
Y1 - 2007/4
N2 - 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 (μMT) mice carrying HLA-DQ8 as transgene, Aβo.DQ8.μmt mice. HLA-DQ8 transgenic mice (Aβo.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 Aβo.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.μmt 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.μmt 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.
AB - 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 (μMT) mice carrying HLA-DQ8 as transgene, Aβo.DQ8.μmt mice. HLA-DQ8 transgenic mice (Aβo.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 Aβo.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.μmt 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.μmt 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.
KW - Antigen presentation
KW - Autoantibodies
KW - B cells
KW - Rheumatoid arthritis
KW - Transgenic/knockout mice
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U2 - 10.1016/j.molimm.2006.12.026
DO - 10.1016/j.molimm.2006.12.026
M3 - Article
C2 - 17303243
AN - SCOPUS:33947124168
SN - 0161-5890
VL - 44
SP - 2988
EP - 2996
JO - Molecular Immunology
JF - Molecular Immunology
IS - 11
ER -