Locus-specific somatic hypermutation in germinal centre T cells

Nature. 1994 Dec 8;372(6506):556-9. doi: 10.1038/372556a0.


Somatic hypermutation and affinity-driven selection of active immunoglobulin genes occur in germinal centres (GCs), resulting in the generation of high-affinity memory B cells. In contrast, T lymphocytes do not require the germinal centre microenvironment to establish memory and the T-cell antigen receptor (TCR) genes, though homologous to immunoglobulin genes, are believed to be incapable of hypermutation. Here we present direct evidence that the small population of antigen-specific T cells that are recruited into splenic GCs acquire mutations in the variable region of genes encoding TCR alpha-chains (V alpha) but not those of beta-chains. These locus-specific mutations reach frequencies comparable to mutated immunoglobulin VH exons recovered from the same site and exhibit similar substitution biases and DNA strand polarity. T cells bearing identical mutations appear in multiple GCs, raising the possibility that some cells bearing mutant TCRs may re-enter the peripheral lymphocyte pool.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Clone Cells
  • DNA, Complementary
  • Genes, Immunoglobulin
  • Immunoenzyme Techniques
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Spleen / cytology*
  • T-Lymphocytes*


  • DNA, Complementary
  • Receptors, Antigen, T-Cell, alpha-beta

Associated data

  • GENBANK/S74150