Novel analysis of clonal diversification in blood B cell and bone marrow plasma cell clones in immunoglobulin light chain amyloidosis.
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.
Abraham
Roshini S
RS
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. abraham.roshini@mayo.edu
Manske
Michelle K
MK
Zuckerman
Neta S
NS
Sohni
Abhishek
A
Edelman
Hanna
H
Shahaf
Gitit
G
Timm
Michael M
MM
Dispenzieri
Angela
A
Gertz
Morie A
MA
Mehr
Ramit
R
D000465:Algorithms; D000686:Amyloidosis / Q000235:genetics* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016130:Immunophenotyping; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*; D016415:Sequence Alignment; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region