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 (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 associa

SUBMITTER: Rydyznski CE 

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

REPOSITORIES: biostudies-literature