| First Author | Munthe LA | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 4 | Pages | 2391-400 |
| PubMed ID | 16081810 | Mgi Jnum | J:107501 |
| Mgi Id | MGI:3621331 | Doi | 10.4049/jimmunol.175.4.2391 |
| Citation | Munthe LA, et al. (2005) Systemic autoimmune disease caused by autoreactive B cells that receive chronic help from Ig V region-specific T cells. J Immunol 175(4):2391-400 |
| abstractText | B cells present BCR V region-derived Id-peptides on their MHC class II molecules to Id-specific CD4+ T cells. Prolonged Id-driven T-B collaboration could cause autoimmune disease, but this possibility is difficult to test in normal individuals. We have investigated whether mice doubly transgenic for an Id+ Ig L chain and an Id-specific TCR develop autoimmune disease. Surprisingly, T cell tolerance was not complete in these mice because a low frequency of weakly Id-reactive CD4+ T cells accumulated with age. These escapee Id-specific T cells provided chronic help for Id+ B cells, resulting in a lethal systemic autoimmune disease including germinal center reactions, hypergammaglobulinemia, IgG autoantibodies, glomerulonephritis, arthritis, skin affection, and inflammatory bowel disease. Inflamed tissues contained foci of Id-driven T-B collaboration, with deposition of IgG and complement. The disease could be transferred with B and T cells. The results demonstrate a novel mechanism for development of autoimmune disease in which self-reactive Id+ B cells receive prolonged help from Id-specific T cells, thus bypassing the need for help from T cells recognizing conventional Ag. |
