| First Author | Tsao PY | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 11 | Pages | 7770-7 |
| PubMed ID | 19017966 | Mgi Jnum | J:142389 |
| Mgi Id | MGI:3821445 | Doi | 10.4049/jimmunol.181.11.7770 |
| Citation | Tsao PY, et al. (2008) T cell-independent spontaneous loss of tolerance by anti-double-stranded DNA B cells in C57BL/6 mice. J Immunol 181(11):7770-7 |
| abstractText | Systemic lupus erythematosus is characterized by loss of tolerance to DNA and other nuclear Ags. To understand the role of T cells in the breaking of tolerance, an anti-DNA site-specific transgenic model of spontaneous lupus, B6x56R, was studied. T cells were eliminated by crossing B6x56R with CD4(-/)(-) or TCRbeta(-/-)delta(-/-) mice, and the effects on anti-dsDNA serum levels, numbers of anti-dsDNA Ab-secreting cells, and isotypes of anti-dsDNA were analyzed. In addition, the development and activation of B cells in these mice were examined. Surprisingly, the presence of T cells made little difference in the development and character of the serum anti-dsDNA Ab in B6x56R mice. At 1 mo of age, anti-dsDNA Abs were somewhat lower in mice deficient in alphabeta and gammadelta T cells. Levels of Abs later were not affected by T cells, nor was autoantibody class switching. B cell activation was somewhat diminished in T cell-deficient mice. Thus, in the B6 background, the presence of an anti-dsDNA transgene led the production of autoantibodies with a specificity and isotype characteristic of murine systemic lupus erythematosus with little influence from T cells. TLR9 also did not appear to play a role. Although we do not yet understand the mechanism of this failure of immunoregulation, these results suggest that similar processes may influence autoimmunity associated with clinical disease. |
