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 language | English |
|---|---|
| Pages (from-to) | 2948-2954 |
| Number of pages | 7 |
| Journal | Blood |
| Volume | 91 |
| Issue number | 8 |
| Publication status | Published - Apr 15 1998 |
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ASJC Scopus subject areas
- Hematology
Cite this
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 journal › Article
}
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.
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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 -