Locus-specific somatic hypermutation in germinal centre T cells.
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.
Zheng
B
B
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201.
Xue
W
W
Kelsoe
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002999:Clone Cells; D018076:DNA, Complementary; D005803:Genes, Immunoglobulin; D007124:Immunoenzyme Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013154:Spleen / Q000166:cytology*; D013601:T-Lymphocytes
D018076:DNA, Complementary; D016693:Receptors, Antigen, T-Cell, alpha-beta