Memory B-cell persistence is independent of persisting immunizing antigen

Nature. 2000 Oct 5;407(6804):636-42. doi: 10.1038/35036600.


Immunological memory in the antibody system is generated in T-cell-dependent responses and carried by long-lived memory B cells that recognize antigen by high-affinity antibodies. But it remains controversial whether these B cells represent true 'memory' cells (that is, their maintenance is independent of the immunizing antigen), or whether they are a product of a chronic immune response driven by the immunizing antigen, which can be retained in the organism for extended time periods on the surface of specialized antigen-presenting cells (follicular dendritic cells). Cell transfer experiments provided evidence in favour of a role of the immunizing antigen; however, analysis of memory cells in intact animals, which showed that these cells are mostly resting and can persist in the absence of detectable T-cell help or follicular dendritic cells, argued against it. Here we show, by using a genetic switch mediated by Cre recombinase, that memory B cells switching their antibody specificity away from the immunizing antigen are indeed maintained in the animal over long periods of time, similar to cells retaining their original antigen-binding specificity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Antibody Specificity
  • Antigens / immunology*
  • B-Lymphocytes / immunology*
  • Cloning, Molecular
  • Genes, Switch
  • Genotype
  • Haptens / immunology
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Immunoglobulin Heavy Chains / genetics
  • Immunologic Memory*
  • Integrases / metabolism
  • Interferon Type I / physiology
  • Molecular Sequence Data
  • Nitrophenols / immunology
  • Phenylacetates
  • Phycoerythrin / immunology
  • Recombination, Genetic
  • Viral Proteins*


  • Antigens
  • Haptens
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Interferon Type I
  • Nitrophenols
  • Phenylacetates
  • Viral Proteins
  • 4-hydroxy-5-nitrophenyl acetic acid
  • Phycoerythrin
  • Cre recombinase
  • Integrases

Associated data

  • GENBANK/AF262991