title: IFN-{gamma} produced by CD8 T cells induces T-bet-dependent and -independent class switching in B cells in responses to alum-precipitated protein vaccine.
abstract: Alum-precipitated protein (alum protein) vaccines elicit long-lasting neutralizing antibody responses that prevent bacterial exotoxins and viruses from entering cells. Typically, these vaccines induce CD4 T cells to become T helper 2 (Th2) cells that induce Ig class switching to IgG1. We now report that CD8 T cells also respond to alum proteins, proliferating extensively and producing IFN-γ, a key Th1 cytokine. These findings led us to question whether adoptive transfer of antigen-specific CD8 T cells alters the characteristic CD4 Th2 response to alum proteins and the switching pattern in responding B cells. To this end, WT mice given transgenic ovalbumin (OVA)-specific CD4 (OTII) or CD8 (OTI) T cells, or both, were immunized with alum-precipitated OVA. Cotransfer of antigen-specific CD8 T cells skewed switching patterns in responding B cells from IgG1 to IgG2a and IgG2b. Blocking with anti-IFN-γ antibody largely inhibited this altered B-cell switching pattern. The transcription factor T-bet is required in B cells for IFN-γ-dependent switching to IgG2a. By contrast, we show that this transcription factor is dispensable in B cells both for IFN-γ-induced switching to IgG2b and for inhibition of switching to IgG1. Thus, T-bet dependence identifies distinct transcriptional pathways in B cells that regulate IFN-γ-induced switching to different IgG isotypes.
authors.affiliation: Medical Research Council Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom. emohr@igc.gulbenkian.pt
authors.forename: Elodie
authors.initials: E
authors.lastname: Mohr
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Kai-Michael
authors.initials: KM
authors.lastname: Toellner
authors.forename: Saeeda
authors.initials: S
authors.lastname: Bobat
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Coughlan
authors.forename: Roger A
authors.initials: RA
authors.lastname: Bird
authors.forename: Ian C M
authors.initials: IC
authors.lastname: MacLennan
authors.forename: Karine
authors.initials: K
authors.lastname: Serre
mesh_terms: D019264:Adoptive Transfer; D000534:Alum Compounds; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000378:metabolism*; D014612:Vaccines / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D000534:Alum Compounds; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014612:Vaccines; C446402:ovalbumin-alum; D007371:Interferon-gamma; D010047:Ovalbumin