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
Journal of Clinical Immunology
Einloggen, um Zugang zu erhalten
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.