Evidence that amyloidogenic light chains undergo antigen-driven selection

Vittorio Perfetti, Paola Ubbiali, Maurizio Colli Vignarelli, Marta Diegoli, Roberta Fasani, Monica Stoppini, Antonella Lisa, Palma Mangione, Laura Obici, Eloisa Arbustini, Giampaolo Merlini

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

AL amyloidosis is characterized by fibrillar tissue deposits (amyloid) composed of monoclonal light chains secreted by small numbers of indolent bone marrow plasma cells whose ontogenesis is unknown. To address this issue and to provide insights into the processes that accompanied pathogenic light chain formation, we isolated the complete variable (V) regions of 14 light (VL) and 3 heavy (VH) chains secreted by amyloid clones at diagnosis (10 Bence Jones and 4 with complete Igs, 9 λ and 5 κ) by using an inverse polymerase chain reaction-based approach free of primer-induced biases. Amyloid V regions were found to be highly mutated compared with the closest germline genes in the databases or those isolated from the patients' DNA, and mutations were not associated with intraclonal diversification. Apparently high usage of the λIII family germline gene V λIII.1 was observed (4 of 9 λ light chains). Analysis of the nature and distribution of somatic mutations in amyloid V regions showed that there was statistical evidence of antigen selection in 8 of 14 clones (7 in VL and 1 in VH). These results indicate that a substantial proportion of the amyloid clones developed from B cells selected for improved antigen binding properties and that pathogenic light chains show evidence of this selection.

Original languageEnglish
Pages (from-to)2948-2954
Number of pages7
JournalBlood
Volume91
Issue number8
Publication statusPublished - Apr 15 1998

Fingerprint

Amyloid
Light
Antigens
Clone Cells
Genes
Mutation
Polymerase chain reaction
Amyloid Plaques
Amyloidosis
Plasma Cells
Bone Marrow Cells
Bone
B-Lymphocytes
Deposits
Cells
Databases
Tissue
Plasmas
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Hematology

Cite this

Perfetti, V., Ubbiali, P., Vignarelli, M. C., Diegoli, M., Fasani, R., Stoppini, M., ... Merlini, G. (1998). Evidence that amyloidogenic light chains undergo antigen-driven selection. Blood, 91(8), 2948-2954.

Evidence that amyloidogenic light chains undergo antigen-driven selection. / Perfetti, Vittorio; Ubbiali, Paola; Vignarelli, Maurizio Colli; Diegoli, Marta; Fasani, Roberta; Stoppini, Monica; Lisa, Antonella; Mangione, Palma; Obici, Laura; Arbustini, Eloisa; Merlini, Giampaolo.

In: Blood, Vol. 91, No. 8, 15.04.1998, p. 2948-2954.

Research output: Contribution to journalArticle

Perfetti, V, Ubbiali, P, Vignarelli, MC, Diegoli, M, Fasani, R, Stoppini, M, Lisa, A, Mangione, P, Obici, L, Arbustini, E & Merlini, G 1998, 'Evidence that amyloidogenic light chains undergo antigen-driven selection', Blood, vol. 91, no. 8, pp. 2948-2954.
Perfetti V, Ubbiali P, Vignarelli MC, Diegoli M, Fasani R, Stoppini M et al. Evidence that amyloidogenic light chains undergo antigen-driven selection. Blood. 1998 Apr 15;91(8):2948-2954.
Perfetti, Vittorio ; Ubbiali, Paola ; Vignarelli, Maurizio Colli ; Diegoli, Marta ; Fasani, Roberta ; Stoppini, Monica ; Lisa, Antonella ; Mangione, Palma ; Obici, Laura ; Arbustini, Eloisa ; Merlini, Giampaolo. / Evidence that amyloidogenic light chains undergo antigen-driven selection. In: Blood. 1998 ; Vol. 91, No. 8. pp. 2948-2954.
@article{aa08290495c84f9289ff6752a5075ee4,
title = "Evidence that amyloidogenic light chains undergo antigen-driven selection",
abstract = "AL amyloidosis is characterized by fibrillar tissue deposits (amyloid) composed of monoclonal light chains secreted by small numbers of indolent bone marrow plasma cells whose ontogenesis is unknown. To address this issue and to provide insights into the processes that accompanied pathogenic light chain formation, we isolated the complete variable (V) regions of 14 light (VL) and 3 heavy (VH) chains secreted by amyloid clones at diagnosis (10 Bence Jones and 4 with complete Igs, 9 λ and 5 κ) by using an inverse polymerase chain reaction-based approach free of primer-induced biases. Amyloid V regions were found to be highly mutated compared with the closest germline genes in the databases or those isolated from the patients' DNA, and mutations were not associated with intraclonal diversification. Apparently high usage of the λIII family germline gene V λIII.1 was observed (4 of 9 λ light chains). Analysis of the nature and distribution of somatic mutations in amyloid V regions showed that there was statistical evidence of antigen selection in 8 of 14 clones (7 in VL and 1 in VH). These results indicate that a substantial proportion of the amyloid clones developed from B cells selected for improved antigen binding properties and that pathogenic light chains show evidence of this selection.",
author = "Vittorio Perfetti and Paola Ubbiali and Vignarelli, {Maurizio Colli} and Marta Diegoli and Roberta Fasani and Monica Stoppini and Antonella Lisa and Palma Mangione and Laura Obici and Eloisa Arbustini and Giampaolo Merlini",
year = "1998",
month = "4",
day = "15",
language = "English",
volume = "91",
pages = "2948--2954",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "8",

}

TY - JOUR

T1 - Evidence that amyloidogenic light chains undergo antigen-driven selection

AU - Perfetti, Vittorio

AU - Ubbiali, Paola

AU - Vignarelli, Maurizio Colli

AU - Diegoli, Marta

AU - Fasani, Roberta

AU - Stoppini, Monica

AU - Lisa, Antonella

AU - Mangione, Palma

AU - Obici, Laura

AU - Arbustini, Eloisa

AU - Merlini, Giampaolo

PY - 1998/4/15

Y1 - 1998/4/15

N2 - AL amyloidosis is characterized by fibrillar tissue deposits (amyloid) composed of monoclonal light chains secreted by small numbers of indolent bone marrow plasma cells whose ontogenesis is unknown. To address this issue and to provide insights into the processes that accompanied pathogenic light chain formation, we isolated the complete variable (V) regions of 14 light (VL) and 3 heavy (VH) chains secreted by amyloid clones at diagnosis (10 Bence Jones and 4 with complete Igs, 9 λ and 5 κ) by using an inverse polymerase chain reaction-based approach free of primer-induced biases. Amyloid V regions were found to be highly mutated compared with the closest germline genes in the databases or those isolated from the patients' DNA, and mutations were not associated with intraclonal diversification. Apparently high usage of the λIII family germline gene V λIII.1 was observed (4 of 9 λ light chains). Analysis of the nature and distribution of somatic mutations in amyloid V regions showed that there was statistical evidence of antigen selection in 8 of 14 clones (7 in VL and 1 in VH). These results indicate that a substantial proportion of the amyloid clones developed from B cells selected for improved antigen binding properties and that pathogenic light chains show evidence of this selection.

AB - AL amyloidosis is characterized by fibrillar tissue deposits (amyloid) composed of monoclonal light chains secreted by small numbers of indolent bone marrow plasma cells whose ontogenesis is unknown. To address this issue and to provide insights into the processes that accompanied pathogenic light chain formation, we isolated the complete variable (V) regions of 14 light (VL) and 3 heavy (VH) chains secreted by amyloid clones at diagnosis (10 Bence Jones and 4 with complete Igs, 9 λ and 5 κ) by using an inverse polymerase chain reaction-based approach free of primer-induced biases. Amyloid V regions were found to be highly mutated compared with the closest germline genes in the databases or those isolated from the patients' DNA, and mutations were not associated with intraclonal diversification. Apparently high usage of the λIII family germline gene V λIII.1 was observed (4 of 9 λ light chains). Analysis of the nature and distribution of somatic mutations in amyloid V regions showed that there was statistical evidence of antigen selection in 8 of 14 clones (7 in VL and 1 in VH). These results indicate that a substantial proportion of the amyloid clones developed from B cells selected for improved antigen binding properties and that pathogenic light chains show evidence of this selection.

UR - http://www.scopus.com/inward/record.url?scp=0032523164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032523164&partnerID=8YFLogxK

M3 - Article

C2 - 9531605

AN - SCOPUS:0032523164

VL - 91

SP - 2948

EP - 2954

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -