期刊
FRONTIERS IN IMMUNOLOGY
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2016.00564
关键词
LCMV; interferon type I; antibody formation; immunopathology; neutralizing antibodies
类别
资金
- Canadian Institutes of Health Research (CIHR) [MOP-89797]
- Natural Sciences and Engineering Research Council of Canada [3559792013]
- Jeanne and J.-Louis Levesque Research Chair in Immunovirology from the J.-Louis Levesque Foundation
- CIHR [MOP-114972]
- Canadian Foundation of Innovation Leaders Opportunity Fund infrastructure grant
Elicitation of type I interferon (IFN-I) has been shown to both enhance and impair cell-mediated immune responses in acute and persistent viral infections, respectively. Here, we show that, in addition to its effect on T cells, IFN-I drives impairment of specific antibody responses through interaction with B cells in the acute phase of lymphocytic choriomeningitis virus (LCMV) infection. This impairment was limited to the T cell-dependent B cell response and was associated with disruption of B cell follicles, development of hypergammaglobulinemia (HGG), and expansion of the T follicular helper cell population. Antigen-specific antibody responses were restored by ablation of IFN-I signaling through antibody-mediated IFN-I receptor blockade and B cell-specific IFN-I receptor knockout. Importantly, IFN-I receptor deficiency in B cells also accelerated the development of LCMV neutralizing antibodies and alleviated HGG. These results provide a potential therapeutic target toward efficient treatment measures that limit immunopathology in persistent viral infections.
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