title: Fas ligand-expressing B-1a lymphocytes mediate CD4(+)-T-cell apoptosis during schistosomal infection: induction by interleukin 4 (IL-4) and IL-10.
abstract: A previous study of the murine model of Schistosoma mansoni infection has implicated splenic CD19(+) B lymphocytes as Fas ligand (FasL)-bearing mediators of CD4(+) T-lymphocyte apoptosis. The present study shows that B-cell deficiency leads to decreased CD4(+) T-cell apoptosis during infection and compares FasL expression and killer function of B-1a- and CD5(-) B-lymphocyte subsets. B-1a cells from uninfected mice displayed constitutive expression of FasL compared with that of CD5(-) B cells. FasL expression was enhanced following worm egg deposition and antigenic stimulation on both subsets of B cells. Purified B-1a cells from uninfected mice were potent effectors of CD4(+) T-cell apoptosis, and the killing effect was enhanced during schistosome infection. FasL expression by splenic B cells required CD4(+)-T-cell help that was replaced by addition of culture supernatants from antigen-stimulated splenocytes of infected mice. The culture-supernatant-stimulated FasL expression was inhibited by anti-interleukin 10 (IL-10) and anti-IL-4 antibodies. Culture of purified B cells with recombinant IL-4 (rIL-4), rIL-10, and soluble egg antigens (SEA) led to increased expression of FasL on B-1a cells. These results suggest that FasL-expressing, splenic B-1a cells are important mediators of SEA-stimulated CD4(+)-T-cell apoptosis and that maximal FasL expression on B-1a cells is dependent on antigenic stimulation and the presence of IL-4 and IL-10.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University, School of Medicine, Detroit, Michigan 48201.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Lundy
authors.forename: Dov L
authors.initials: DL
authors.lastname: Boros
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018956:CD5 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005260:Female; D015801:Helminth Proteins; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000097:blood / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D014407:Tumor Cells, Cultured
chemical_list: D018941:Antigens, CD19; D000947:Antigens, Helminth; D015415:Biomarkers; D018956:CD5 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D015801:Helminth Proteins; D007376:Interleukin-2; D008562:Membrane Glycoproteins; C055560:p40 egg antigen, Schistosoma; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma