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Origin and Pathogenesis of B Cell Lymphomas.

Marc Seifert1, René Scholtysik1, Ralf Küppers2

  • 1Institute of Cell Biology (Cancer Research), Medical School, University of Duisburg-Essen, Nordrhein-Westfalen, Essen, Germany.

Methods in Molecular Biology (Clifton, N.J.)
|February 20, 2019
PubMed
Summary

Errors in immunoglobulin gene remodeling during B cell development can lead to B cell lymphomas. These errors, along with other genetic and environmental factors, contribute to the development and growth of these cancers.

Keywords:
B cell lymphomaB cellsChromosomal translocationClonalityGerminal centerHodgkin lymphomaImmunoglobulin genesSomatic hypermutationV gene recombination

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Area of Science:

  • Immunology
  • Oncology
  • Genetics

Background:

  • Immunoglobulin (IG) gene remodeling via V(D)J recombination is crucial for normal B cell development.
  • Somatic hypermutation and class switching are key to antigen-driven B cell differentiation.
  • Errors in these IG gene processes contribute to B cell lymphomas.

Purpose of the Study:

  • To elucidate the mechanisms underlying B cell lymphoma development.
  • To identify genetic and environmental factors contributing to B cell malignancies.
  • To understand the role of IG gene processes in B cell transformation.

Main Methods:

  • Analysis of V(D)J recombination and IG gene mutation processes.
  • Investigation of IG locus translocations and proto-oncogene activation.
  • Evaluation of tumor suppressor gene mutations and viral infections (e.g., Epstein-Barr virus).
  • Assessment of B cell antigen receptor expression and chronic antigenic stimulation.
  • Study of microenvironmental influences on lymphoma pathophysiology.

Main Results:

  • Errors in IG gene remodeling are implicated in B cell lymphoma development.
  • IG locus translocations involving proto-oncogenes are common in B cell malignancies.
  • Mutations in tumor suppressor genes and viral infections (Epstein-Barr virus) are additional transforming events.
  • B cell antigen receptor expression and chronic antigenic stimulation can drive lymphoma growth.
  • Microenvironmental signals are critical for lymphoma survival and proliferation.
  • Germinal center B cells are a frequent origin of B cell malignancies due to high proliferation and mutation rates.

Conclusions:

  • Dysregulation of normal B cell processes, including IG gene remodeling, is central to B cell lymphoma pathogenesis.
  • Multiple genetic alterations, viral infections, and microenvironmental factors converge to drive B cell malignancies.
  • Targeting these aberrant processes and factors holds potential for therapeutic strategies against B cell lymphomas.