Analysis of Somatic Hypermutation and Antigenic Selection in the Clonal B Cell in Immunoglobulin Light Chain Amyloidosis (AL)

Overview

Journal J Clin Immunol

Publisher Springer

Specialty Allergy & Immunology

Date 2004 May 28

PMID 15163890

Citations 7

Authors

Roshini S Abraham

Susan M Geyer

Marina Ramirez-Alvarado

Tammy L Price-Troska

Morie A Gertz

Rafael Fonseca

Affiliations

Soon will be listed here.

Abstract

Light chain amyloidosis (AL) is a protein folding disorder with an underlying B cell neoplasia where the monoclonal immunoglobulin light chains (LCs) produced from insoluble amyloid fibrils. The deposition of these fibrillar aggregates in vital organs causes severe organ dysfunction over time and is associated with high mortality. We have identified the postgerminal center status of the B cell clone by evaluating the presence of somatic hypermutation in the variable region of the LC gene in 27 (13 of the lambda and 14 of the kappa subtype) AL patients. Seven of the 27 clones showed statistically significant evidence of antigenic selection, using a multinomial algorithm. The framework region mutations were selected for conservation of protein structure in 13 of the 27 patients. Additionally, mutational clusterspots were identified at specific positions in the nucleotide and deduced protein sequence that could potentially contribute to destabilizing interactions resulting in a propensity to form amyloid.

Citing Articles

Role of the mechanisms for antibody repertoire diversification in monoclonal light chain deposition disorders: when a friend becomes foe.

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Molecular mechanism of amyloidogenic mutations in hypervariable regions of antibody light chains.

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Seeded fibrils of the germline variant of human λ-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stability.

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Different Dynamics in 6aJL2 Proteins Associated with AL Amyloidosis, a Conformational Disease.

Maya-Martinez R, French-Pacheco L, Valdes-Garcia G, Pastor N, Amero C Int J Mol Sci. 2019; 20(17).

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Immunoglobulin light chain amyloid aggregation.

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