期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 40, 页码 17292-17297出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1004879107
关键词
B-cell Ig class switch; T helper 1 cells; T helper 2 cells; IgG2a; IgG2b
资金
- British Medical Research Council
- Leverhulme Trust
- Wellcome Trust
- European Union
- Biomedical Services Unit at University of Birmingham
- MRC [G0701275, G9818340, G8402371] Funding Source: UKRI
- Medical Research Council [G8402371, G9818340, G0701275, G9818340B] Funding Source: researchfish
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.
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