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Somatic hypermutation in normal and transformed human B cells

U Klein1, T Goossens, M Fischer

  • 1Institute for Genetics, University of Cologne, Germany.

Immunological Reviews
|May 29, 1998
PubMed
Summary
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Regulation of immunoglobulin light chain gene rearrangements during early B cell development in the human.

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Most human B-cell lymphomas, including Hodgkin

Area of Science:

  • Immunology and Cancer Biology
  • Hematology

Background:

  • Peripheral blood B cells (IgM+IgD+ and CD5+) are typically pre-germinal center (GC) with unmutated V genes.
  • Memory B cells, generated in the GC, have somatically mutated V-region genes and include class-switched, IgM-only, and CD27+IgM+IgD+ subsets.

Purpose of the Study:

  • To identify the developmental stage of progenitor cells in human B-cell lymphomas.
  • To compare rearranged V-region genes of lymphomas with normal B-cell subsets to determine tumor origins.

Main Methods:

  • Analysis of rearranged V-region genes from human B-cell lymphomas.
  • Comparison with V-region genes from normal human B-cell subsets.
  • Sequence analysis of rearranged V genes from single tonsillar germinal center B cells.

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Main Results:

  • Most B-cell non-Hodgkin lymphomas and Hodgkin/Reed-Sternberg (HRS) cells originate from GC or post-GC B cells.
  • Tumor precursors are selected for functional antigen receptors, except for HRS cells in classical Hodgkin's disease, which appear 'crippled'.
  • Somatic hypermutation introduces deletions/insertions into V-region genes more frequently than previously thought.

Conclusions:

  • B-cell lymphomas and Hodgkin's disease arise from germinal center-derived B cells.
  • The frequent introduction of deletions/insertions during somatic hypermutation may explain heavy chain disease and oncogene translocations in lymphomas.