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Related Experiment Videos

Locus-specific somatic hypermutation in germinal centre T cells

B Zheng1, W Xue, G Kelsoe

  • 1Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201.

Nature
|December 8, 1994
PubMed
Summary
This summary is machine-generated.

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T cells recruited into germinal centers (GCs) acquire mutations in their T-cell receptor (TCR) alpha-chain genes, similar to B cells. These findings challenge the long-held belief that TCR genes are incapable of hypermutation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Germinal centers (GCs) are crucial microenvironments for B cell maturation, involving somatic hypermutation and affinity selection of immunoglobulin genes.
  • T lymphocytes establish memory independently of GCs, and their T-cell receptor (TCR) genes were thought to be incapable of hypermutation.

Purpose of the Study:

  • To investigate whether T cells within germinal centers undergo gene mutations in their T-cell receptor (TCR) genes.
  • To compare the mutation patterns in TCR genes with those of immunoglobulin genes within the GC environment.

Main Methods:

  • Analysis of antigen-specific T cells recruited into splenic germinal centers.
  • Sequencing of variable region genes encoding TCR alpha-chains (Vα) and beta-chains (Vβ).

Related Experiment Videos

  • Comparison of mutation frequencies, substitution biases, and DNA strand polarity with immunoglobulin VH exons.

    • Main Results:

    • A small population of antigen-specific T cells in splenic GCs acquired mutations in Vα genes, but not in Vβ genes.
    • The observed locus-specific mutations in TCR genes occurred at frequencies comparable to mutated immunoglobulin VH exons from the same site.
    • Identical mutations were found in T cells across multiple GCs, suggesting potential clonal expansion or migration.

    Conclusions:

    • Direct evidence demonstrates that TCR alpha-chain genes can undergo somatic hypermutation within germinal centers.
    • These findings challenge the established understanding of T-cell memory formation and TCR gene stability.
    • The presence of identical mutations in multiple GCs suggests that T cells with mutated TCRs may recirculate in the peripheral lymphocyte pool.