| First Author | Keech CL | Year | 2001 |
| Journal | J Immunol | Volume | 166 |
| Issue | 9 | Pages | 5826-34 |
| PubMed ID | 11313427 | Mgi Jnum | J:134705 |
| Mgi Id | MGI:3789549 | Doi | 10.4049/jimmunol.166.9.5826 |
| Citation | Keech CL, et al. (2001) Cognate T cell help is sufficient to trigger anti-nuclear autoantibodies in naive mice. J Immunol 166(9):5826-34 |
| abstractText | The mechanisms involved in the initiation of anti-nuclear autoantibodies are unknown. In this study, we show that one factor allowing anti-nuclear autoantibodies to develop is the incomplete nature of immune tolerance to many of these proteins. Immune responses in mice toward the ubiquitous nuclear autoantigen La/SS-B are much weaker than responses to the xenoantigen, human La (hLa; 74% identical). However, in transgenic (Tg) mice expressing hLa, the Ab response to this neo-autoantigen was reduced to a level resembling the weak autoimmune response to mouse LA: Partial tolerance to endogenous La autoantigen was restricted to the T compartment because transfer of CD4(+) T cells specific for one or more hLa determinants into mice bearing the hLa transgene was sufficient to elicit production of anti-hLa autoantibodies. Notably, only hLa- specific T cells from non-Tg mice, and not T cells from hLa Tg mice, induced autoantibody production in hLa Tg mice. These findings confirm partial Th tolerance to endogenous La and indicate the existence in normal animals of autoreactive B cells continuously presenting La nuclear AG: Therefore, the B cell compartment is constitutively set to respond to particular nuclear autoantigens, implicating limiting Th responses as a critical checkpoint in the development of anti-nuclear autoantibodies in normal individuals. |
