title: Trypanosoma cruzi infection selectively renders parasite-specific IgG+ B lymphocytes susceptible to Fas/Fas ligand-mediated fratricide.
abstract: The control of B cell expansion has been thought to be solely regulated by T lymphocytes. We show in this study that Trypanosoma cruzi infection induces up-regulation of both Fas and Fas ligand (FasL) molecules on B cells and renders them susceptible to B cell-B cell killing (referred to as fratricide throughout this paper) mediated via Fas/FasL. Moreover, by in vivo administration of anti-FasL blocking mAb we demonstrate that Fas-mediated B cell apoptosis is an ongoing process during this parasitic infection. We also provide evidence that B cells that have switched to IgG isotype are the preferential targets of B cell fratricide. More strikingly, this death pathway selectively affects IgG(+) B cells reactive to parasite but not self Ags. Parasite-specific but not self-reactive B cells triggered during this response are rescued after either in vitro or in vivo FasL blockade. Fratricide among parasite-specific IgG(+) B lymphocytes could impair the immune control of T. cruzi and possibly other chronic protozoan parasites. Our results raise the possibility that the blockade of Fas/FasL interaction in the B cell compartment of T. cruzi-infected mice may provide a means for enhancing antiparasitic humoral immune response without affecting host tolerance.
authors.affiliation: Department of Clinical Biochemistry, Faculty of Chemical Science, National University of Cordoba, Cordoba, Argentina.
authors.forename: Elina
authors.initials: E
authors.lastname: Zuñiga
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Motran
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Montes
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Adriana
authors.initials: A
authors.lastname: Gruppi
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000921:Antibody-Producing Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D000953:Antigens, Protozoan / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology* / Q000473:pathology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D053222:Fas Ligand Protein; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*; D019014:fas Receptor / Q000502:physiology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor