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.
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Related Subject Headings
- T-Lymphocytes
- Spleen
- Receptors, Antigen, T-Cell, alpha-beta
- Mutation
- Molecular Sequence Data
- Mice
- Immunoenzyme Techniques
- Genes, Immunoglobulin
- General Science & Technology
- DNA, Complementary
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- T-Lymphocytes
- Spleen
- Receptors, Antigen, T-Cell, alpha-beta
- Mutation
- Molecular Sequence Data
- Mice
- Immunoenzyme Techniques
- Genes, Immunoglobulin
- General Science & Technology
- DNA, Complementary