Class-switched memory B cells remodel BCRs within secondary germinal centers

Nat Immunol. 2015 Mar;16(3):296-305. doi: 10.1038/ni.3095. Epub 2015 Feb 2.

Abstract

Effective vaccines induce high-affinity memory B cells and durable antibody responses through accelerated mechanisms of natural selection. Secondary changes in antibody repertoires after vaccine boosts suggest progressive rediversification of B cell receptors (BCRs), but the underlying mechanisms remain unresolved. Here, the integrated specificity and function of individual memory B cell progeny revealed ongoing evolution of polyclonal antibody specificities through germinal center (GC)-specific transcriptional activity. At the clonal and subclonal levels, single-cell expression of the genes encoding the costimulatory molecule CD83 and the DNA polymerase Polη segregated the secondary GC transcriptional program into four stages that regulated divergent mechanisms of memory BCR evolution. Our studies demonstrate that vaccine boosts reactivate a cyclic program of GC function in class-switched memory B cells to remodel existing antibody specificities and enhance durable immunological protection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibody Formation / immunology
  • Antigens, CD / immunology
  • B-Lymphocytes / immunology*
  • DNA-Directed DNA Polymerase / immunology
  • Germinal Center / immunology*
  • Immunoglobulin Class Switching / immunology
  • Immunoglobulins / immunology
  • Immunologic Memory / immunology*
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, B-Cell / immunology*
  • Transcription, Genetic / immunology

Substances

  • Antibodies
  • Antigens, CD
  • CD83 antigen
  • Immunoglobulins
  • Membrane Glycoproteins
  • Receptors, Antigen, B-Cell
  • DNA-Directed DNA Polymerase