Mechanism of antigen-driven selection in germinal centres

Nature. 1989 Dec 21-28;342(6252):929-31. doi: 10.1038/342929a0.

Abstract

The high affinity of antibodies produced during responses to T-cell-dependent antigens is associated with somatic mutation in the variable region of the immunoglobulin. Indirect evidence indicates that: (1) this arises by a process of hypermutation, acting selectively on rearranged immunoglobulin variable-region genes, which is activated in centroblasts within germinal centres; and (2) centrocytes, the progeny of centroblasts, undergo selection on the basis of their ability to receive a positive signal from antigen. We have now performed experiments analysing this selection process, and found that, on culture, centrocytes isolated from human tonsil kill themselves within a few hours by apoptosis. This is not a feature of other tonsillar B cells. Centrocytes can be prevented from entering apoptosis if they are activated both through their receptors for antigen and a surface glycoprotein recognized by CD40 antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / immunology*
  • Antigens, CD / immunology*
  • Antigens, Surface / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Survival
  • Cells, Cultured
  • Culture Techniques / methods
  • Cytotoxicity, Immunologic
  • Humans
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology
  • Phenotype

Substances

  • Antibodies
  • Antigens, CD
  • Antigens, Surface