Nodal marginal zone B-cell lymphomas may arise from different subsets of marginal zone B lymphocytes

Blood. 2001 Aug 1;98(3):781-6. doi: 10.1182/blood.v98.3.781.

Abstract

Nodal marginal zone B-cell lymphoma (MZL) is a rare and not extensively studied entity that accounts for approximately 2% of all non-Hodgkin lymphomas. Complementarity-determining regions 2 and 3 (CDR2, CDR3) of the immunoglobulin heavy-chain variable region (V(H)) genes were amplified by polymerase chain reaction (PCR), cloned, and sequenced in 8 patients with nodal MZL. All showed a potentially functional V(H) rearrangement. The use of V(H) gene families was unbiased and without overrepresentation of any particular V(H) gene or gene family. The presence of somatic V(H) mutations was detected, with a deviation from the closest germ line sequence ranging from 4% to 17% in 6 of 8 patients. In 3 mutations, the replacement-to-silent mutation ratio suggested the presence of an antigen-selected process. Sequencing different subclones of the same cloned PCR products allowed the detection of intraclonal variability in 4 analyzed patients. The observed pattern of V(H) mutations suggested that nodal MZL, formerly deemed a malignancy of memory B cells, may arise from different subsets of marginal zone B cells-the naive B cells that express unmutated V(H) genes-from memory B cells showing somatic mutations without intraclonal variation, and from germinal center B cells defined by their capacity to undergo the somatic hypermutation process. (Blood. 2001;98:781-786)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Cloning, Molecular
  • Complementarity Determining Regions / genetics
  • Female
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / immunology
  • Immunophenotyping
  • Lymph Nodes / pathology
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / pathology
  • Lymphoma, B-Cell / etiology*
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell, Marginal Zone / etiology*
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / immunology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Sequence Analysis, DNA

Substances

  • Complementarity Determining Regions
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region