Novel analysis of clonal diversification in blood B cell and bone marrow plasma cell clones in immunoglobulin light chain amyloidosis

J Clin Immunol. 2007 Jan;27(1):69-87. doi: 10.1007/s10875-006-9056-9. Epub 2006 Dec 28.

Abstract

Immunoglobulin light chain amyloidosis (AL) is characterized by a limited clonal expansion of plasma cells and amyloid formation. Here, we report restriction in the diversity of VL gene usage with a dominance of clonally related B cells in the peripheral blood (PB) isotype-specific repertoire of AL patients. A rigorous quantification of lineage trees reveals presence of intraclonal variations in the PB clones compared to the bone marrow (BM) clones, which suggests a common precursor that is still subject to somatic mutation. When compared to normal BM and PB B cells, AL clones showed significant but incomplete impairment of antigenic selection, which could not be detected by conventional R and S mutation analysis. Therefore, graphical analysis of B cell lineage trees and mathematical quantification of tree properties provide novel insights into the process of B cell clonal evolution in AL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amyloidosis / genetics*
  • Amyloidosis / immunology*
  • Bone Marrow Cells / immunology
  • Clone Cells / immunology
  • Female
  • Flow Cytometry
  • Genes, Immunoglobulin*
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Light Chains / genetics*
  • Immunoglobulin Variable Region / genetics*
  • Immunophenotyping
  • Male
  • Models, Biological
  • Molecular Sequence Data
  • Multiple Myeloma / genetics
  • Multiple Myeloma / immunology
  • Plasma Cells / immunology*
  • Sequence Alignment
  • Somatic Hypermutation, Immunoglobulin / genetics

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region