The influence of effector T cells and Fas ligand on lupus-associated B cells.
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.
Fields
Michele L
ML
The Wistar Institute, Room 276, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Nish
Simone A
SA
Hondowicz
Brian D
BD
Metzgar
Michele H
MH
Wharton
Gina N
GN
Caton
Andrew J
AJ
Erikson
Jan
J
D019264:Adoptive Transfer; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D002843:Chromatin / Q000276:immunology; D053222:Fas Ligand Protein; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008211:Lymphocyte Cooperation; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000974:Antibodies, Antinuclear; D002843:Chromatin; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007145:Immunoglobulin kappa-Chains; D008562:Membrane Glycoproteins