Affinity Maturation Is Impaired by Natural Killer Cell Suppression of Germinal Centers.
Cell Rep
; 24(13): 3367-3373.e4, 2018 09 25.
Article
in En
| MEDLINE
| ID: mdl-30257198
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Killer Cells, Natural
/
Germinal Center
/
Somatic Hypermutation, Immunoglobulin
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2018
Document type:
Article
Affiliation country:
United States