| First Author | Khmaladze Ia | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 8 | Pages | 2243-51 |
| PubMed ID | 25989352 | Mgi Jnum | J:229744 |
| Mgi Id | MGI:5754418 | Doi | 10.1002/eji.201545518 |
| Citation | Khmaladze Ia, et al. (2015) B-cell epitope spreading and inflammation in a mouse model of arthritis is associated with a deficiency in reactive oxygen species production. Eur J Immunol 45(8):2243-51 |
| abstractText | Autoantibody-mediated inflammation contributes to the development of rheumatoid arthritis (RA), and anti-type II collagen (CII) antibodies are present in the serum, synovial fluid, and cartilage of RA patients. We had previously generated and characterized knock-in mice expressing a germline-encoded, CII-specific IgH (B10Q.ACB), which demonstrated positive selection of self-reactive B cells. Here, we show that despite the spontaneous production of CII-specific autoantibodies, B10Q.ACB mice are protected from collagen-induced arthritis. Introducing a mutation in the Ncf1 gene, leading to ROS deficiency, breaks this strong arthritis resistance. Disease development in Ncf1-mutated B10Q.ACB mice is associated with an enhanced germinal center formation but without somatic mutations of the auto-reactive B cells, increased T-cell responses and intramolecular epitope-spreading. Thus, ROS-mediated B-cell tolerance to a self-antigen could operate by limiting the expansion of the auto-reactive B-cell repertoire, which has important implications for the understanding of epitope spreading phenomena in rheumatoid arthritis and other autoimmune diseases. |
