期刊
CELL REPORTS
卷 24, 期 13, 页码 3367-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.08.075
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资金
- NIH [AR047363, AR070549, DK078392, DK090971, AI104739, AI118179, DA038017]
- Lawrence Ellison Foundation
- Cincinnati Children's Research Foundation
- Albert J. Ryan Fellowship Program
- Gruber Science Fellowship
Somatic hypermutation of immunoglobulin sequences in germinal center (GC) reactions must be optimized to elicit high-affinity, protective antibodies after vaccination. We expose natural killer (NK) cells as robust negative regulators of somatic hypermutation in antigen-reactive B cells. NK cells restrict follicular helper T cell (T-FH) and GC B cell frequencies and titers of antigen-specific immunoglobulin after administration of alum-adjuvanted hapten-protein conjugate vaccines. This inhibition is perforin dependent, suggesting that NK cells kill one or more cells critical for GC development. In the presence of perforin-competent NK cells, antigen-specific GC B cells acquire fewer mutations, including less frequent generation of non-synonymous substitutions and mutations associated with increased antibody affinity. Thus, NK cells limit the magnitude of GC reactions and thereby restrain vaccine elicitation of high-affinity antibodies. Circumventing this activity of NK cells during vaccination has strong potential to enhance humoral immunity and facilitate vaccine-elicited prevention of disease.
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