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

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-[gamma], 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-[gamma] antibody largely inhibited this altered B-cell switching pattern. The transcription factor T-bet is required in B cells for IFN-[gamma]--dependent switching to IgG2a. By contrast, we show that this transcription factor is dispensable in B cells both for IFN-[gamma]--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-[gamma]--induced switching to different IgG isotypes. B-cell Ig class switch | T helper 1 cells | T helper 2 cells | IgG2a | IgG2b doi/ 10.1073/pnas.1004879107