Unknown

Dataset Information

0

Affinity Maturation Is Impaired by Natural Killer Cell Suppression of Germinal Centers.


ABSTRACT: 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 (TFH) 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.

SUBMITTER: Rydyznski CE 

PROVIDER: S-EPMC6192537 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4938154 | biostudies-literature
| S-EPMC2195593 | biostudies-literature
2022-09-15 | GSE209904 | GEO
2022-09-19 | GSE213361 | GEO
| S-EPMC3890789 | biostudies-literature
| S-EPMC5940267 | biostudies-literature
| S-EPMC7479651 | biostudies-literature
| S-EPMC2254552 | biostudies-literature
| S-EPMC7478071 | biostudies-literature
| S-EPMC4364831 | biostudies-other