title: Antioxidant treatment regulates the humoral immune response during acute viral infection.
abstract: Generation of reactive oxygen intermediates (ROI) following antigen receptor ligation is critical to promote cellular responses. However, the effect of antioxidant treatment on humoral immunity during a viral infection was unknown. Mice were infected with lymphocytic choriomeningitis virus (LCMV) and treated with Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), a superoxide dismutase mimetic, from days 0 to 8 postinfection. On day 8, at the peak of the splenic response in vehicle-treated mice, virus-specific IgM and IgG antibody-secreting cells (ASC) were decreased 22- and 457-fold in MnTBAP-treated animals. By day 38, LCMV-specific IgG ASC were decreased 5-fold in the bone marrow of drug-treated mice, and virus-specific antibodies were of lower affinity. Interestingly, antioxidant treatment had no effect on the number of LCMV-specific IgG memory B cells. In addition to decreases in ASC, MnTBAP treatment decreased the number of functional virus-specific CD4(+) T cells. The decreased numbers of ASC observed on day 8 in drug-treated mice were due to a combination of Bim-mediated cell death and decreased proliferation. Together, these data demonstrate that ROI regulate antiviral ASC expansion and have important implications for understanding the effects of antioxidants on humoral immunity during infection and immunization.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Katie E
authors.initials: KE
authors.lastname: Crump
authors.forename: P Kent
authors.initials: PK
authors.lastname: Langston
authors.forename: Sujana
authors.initials: S
authors.lastname: Rajkarnikar
authors.forename: Jason M
authors.initials: JM
authors.lastname: Grayson
mesh_terms: D000208:Acute Disease; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001117:Arenaviridae Infections / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D001854:Bone Marrow Cells / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D019610:Cytoprotection; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D056724:Immunity, Humoral / Q000187:drug effects*; D007156:Immunologic Memory; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D016166:Free Radical Scavengers; D008565:Membrane Proteins; D008665:Metalloporphyrins; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin