Journal of Clinical Immunology

, Volume 27, Issue 1, pp 69–87 | Cite as

Novel Analysis of Clonal Diversification in Blood B Cell and Bone Marrow Plasma Cell Clones in Immunoglobulin Light Chain Amyloidosis

  • ROSHINI S. ABRAHAM
  • MICHELLE K. MANSKE
  • NETA S. ZUCKERMAN
  • ABHISHEK SOHNI
  • HANNA EDELMAN
  • GITIT SHAHAF
  • MICHAEL M. TIMM
  • ANGELA DISPENZIERI
  • MORIE A. GERTZ
  • RAMIT MEHR
Article

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.

KEY WORDS

Human B cells cell differentiation repertoire development plasma cells light chain amyloidosis immunoglobulin light chain 

Notes

ACKNOWLEDGMENTS

The authors acknowledge the Mayo Dysproteinemia Cell Bank for providing BM and blood samples for the AL and MM patients. The authors thank Michal Barak and Avital Steiman for critical reading of the manuscript, and Ms. Lavonne Knutson for assistance with manuscript preparation. The authors would like to acknowledge the following sources of financial support for this study: the Hematological Malignancies Research Fund (RSA), the Israel Science Foundation (grant number 759/01-1), the Israel Cancer Research Fund, the Human Frontiers Science Program, and the Swedish Foundation for Strategic Research (RM).

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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • ROSHINI S. ABRAHAM
    • 1
    • 6
  • MICHELLE K. MANSKE
    • 2
  • NETA S. ZUCKERMAN
    • 3
  • ABHISHEK SOHNI
    • 4
  • HANNA EDELMAN
    • 3
  • GITIT SHAHAF
    • 3
  • MICHAEL M. TIMM
    • 2
  • ANGELA DISPENZIERI
    • 5
  • MORIE A. GERTZ
    • 5
  • RAMIT MEHR
    • 3
  1. 1.Department of Laboratory Medicine and PathologyMayo Clinic College of MedicineRochesterUSA
  2. 2.Hematology Research LaboratoryMayo ClinicRochesterUSA
  3. 3.Faculty of Life SciencesBar-Ilan UniversityRamat-GanIsrael
  4. 4.Genetics, Cell and Developmental BiologyUniversity of MinnesotaMinnesotaUSA
  5. 5.Division of HematologyMayo Clinic College of MedicineRochesterUSA
  6. 6.Department of Laboratory Medicine and PathologyHilton 210 e, Mayo Clinic College of MedicineRochesterUSA

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