The Influence of Effector T Cells and Fas Ligand on Lupus-Associated B Cells

The Wistar Institute, Room 276, 3601 Spruce Street, Philadelphia, PA 19104, USA.
The Journal of Immunology (Impact Factor: 4.92). 08/2005; 175(1):104-11. DOI: 10.4049/jimmunol.175.1.104
Source: PubMed


Circulating autoantibodies against dsDNA and chromatin are a characteristic of systemic lupus erythematosus in humans and many mouse models of this disease. B cells expressing these autoantibodies are normally regulated in nonautoimmune-prone mice but are induced to secrete Abs following T cell help. Likewise, anti-chromatin autoantibody production is T cell-dependent in Fas/Fas ligand (FasL)-deficient (lpr/lpr or gld/gld) mice. In this study, we demonstrate that Th2 cells promote anti-chromatin B cell survival and autoantibody production in vivo. FasL influences the ability of Th2 cells to help B cells, as Th2-gld/gld cells support higher titers of anti-chromatin Abs than their FasL-sufficient counterparts and promote anti-chromatin B cell participation in germinal centers. Th1 cells induce anti-chromatin B cell germinal centers regardless of FasL status; however, their ability to stimulate anti-chromatin Ab production positively correlates with their level of IFN-gamma production. This distinction is lost if FasL-deficient T cells are used: Th1-gld/gld cells promote significant titers of anti-chromatin Abs regardless of IFN-gamma production levels. Thus, FasL from effector T cells plays an important role in determining the fate of anti-chromatin B cells.

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Available from: Michele L Fields, Nov 05, 2014
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    • "The importance of T cell-B cell interaction has been demonstrated in lupus-prone MRL-lpr animals lacking CD4 + or ab T cells, because these animals have delayed, less-severe disease and reduced autoantibody titers (Connolly et al., 1992; Peng, 1998; Peng et al., 1996b). Conversely, the addition of autoreactive T cells to preautoimmune or nonautoimmune mice has led to autoreactive B cell activation and autoantibody secretion (Adams et al., 1991; Ando et al., 1987; Fields et al., 2005b) and even loss of anergic features (Seo et al., 2002). Although the nature of these B cell-T cell interactions is still not clarified, it is reasonable to think that the same types of B cells that generate cardinal autoantibodies are also providing activation signals to T cells that recognize cognate autoantigens. "
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    • "Our results are supported by previous studies indicating that systemic FK506 treatment of mice is able to decrease serum levels of anti-DNA antibodies (Sugiyama et al., 2004). Because the numbers of CD19 þ B cells are not significantly reduced in FK506- injected CD40L tg mice compared to the PBS-treated control group, it is possible that the reduced production of antinuclear antibodies could be a consequence of impaired Th function as T cells can provide help to B cells (Fields et al., 2005). Alternatively, FK506 may also be able to influence B cell function directly. "
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