Clonal selection and learning in the antibody system

Nature. 1996 Jun 27;381(6585):751-8. doi: 10.1038/381751a0.


Each antibody-producing B cell makes antibodies of unique specificity, reflecting a series of ordered gene rearrangements which must be successfully performed if the cell is to survive. A second selection process occurs during immune responses in which a new antibody repertoire is generated through somatic hypermutation. Here only mutants binding antigen with high affinity survive to become memory cells. Cells expressing autoreactive receptors are counter-selected at both stages. This stringent positive and negative selection allows the generation and diversification of cells while rigorously controlling their specificity.

Publication types

  • Review

MeSH terms

  • Alleles
  • Animals
  • Antibody Formation / genetics
  • Antibody Formation / physiology*
  • Antibody Specificity
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Chickens
  • Clone Cells
  • Hematopoiesis / physiology
  • Humans
  • Immune Tolerance / immunology
  • Immunoglobulin Variable Region / genetics
  • Immunologic Memory
  • Mutation
  • Receptors, Antigen, B-Cell / physiology


  • Immunoglobulin Variable Region
  • Receptors, Antigen, B-Cell