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

• Published in: The Journal of immunology (1950) Vol. 175; no. 1; pp. 104 - 111
• Main Authors: Fields, Michele L, Nish, Simone A, Hondowicz, Brian D, Metzgar, Michele H, Wharton, Gina N, Caton, Andrew J, Erikson, Jan
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.07.2005
• Subjects: Adoptive Transfer; Animals; Antibodies, Antinuclear - biosynthesis; B-Lymphocytes - immunology; Chromatin - immunology; Fas Ligand Protein; Humans; Immunoglobulin kappa-Chains - genetics; Immunoglobulin kappa-Chains - metabolism; In Vitro Techniques; Lupus Erythematosus, Systemic - immunology; Lymphocyte Cooperation; Membrane Glycoproteins - immunology; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Th1 Cells - immunology; Th2 Cells - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.175.1.104

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.