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.
| Original language | English |
|---|---|
| Pages (from-to) | 69-87 |
| Number of pages | 19 |
| Journal | Journal of Clinical Immunology |
| Volume | 27 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2007 |
Bibliographical note
Funding Information: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).
Funding
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).
| Funders | Funder number |
|---|---|
| Israel Cancer Research Fund | |
| Human Frontier Science Program | |
| Stiftelsen för Strategisk Forskning | |
| Israel Science Foundation | 759/01-1 |
Keywords
- B cells
- Cell differentiation
- Human
- Immunoglobulin light chain
- Light chain amyloidosis
- Plasma cells
- Repertoire development