| First Author | Yan J | Year | 2002 |
| Journal | Int Immunol | Volume | 14 |
| Issue | 8 | Pages | 963-71 |
| PubMed ID | 12147633 | Mgi Jnum | J:131498 |
| Mgi Id | MGI:3773814 | Doi | 10.1093/intimm/dxf064 |
| Citation | Yan J, et al. (2002) B and T cell tolerance and autoimmunity in autoantibody transgenic mice. Int Immunol 14(8):963-71 |
| abstractText | One hallmark of systemic lupus erythematosus (SLE) is the presence of autoantibodies directed at a diverse group of proteins of the U1/Sm small nuclear ribonucleoprotein particles (snRNP). Patients with SLE and murine models of this disease generate high titers of affinity mature, isotype-switched autoantibodies characteristic of T cell-dependent immune responses. In this investigation, we made use of anti-snRNP Ig transgenic mice (2-12 Tg) to track regulation of autoreactive B cells in normal and autoimmune-prone mice. Autoantibody studies demonstrated that the regulation of anti-snRNP B cells is intact in non-autoimmune Tg mice, but not in MRL-lpr/lpr mice. We further utilize autoreactive Tg B cells as antigen-presenting cells (APC) and individual snRNP peptides to assess the presence of autoreactive T cells in the repertoire of non-autoimmune and MRL-lpr/lpr mice. We found that Tg B cells can direct specific T cell tolerance in a non-autoimmune-prone (C57Bl/6) background, whereas the same autoantibody transgene in MRL-lpr/lpr mice drives T cell autoimmunity. Moreover, Tg B cell APC could stimulate autoreactive T cells from wild-type (non-Tg) C57Bl/6 mice, indicating a lack of tolerance induction in the absence of the autoantigenic-presenting B cells. Thus, we have defined dual roles for autoantigen-presenting B lymphocytes in stimulating self-reactive T cells that inhabit the normal repertoire or, under some conditions, providing tolerance signals. |
