EVIDENCE THAT AMYLOIDOGENIC LIGHT-CHAINS UNDERGO ANTIGEN-DRIVEN SELECTION

Citation
V. Perfetti et al., EVIDENCE THAT AMYLOIDOGENIC LIGHT-CHAINS UNDERGO ANTIGEN-DRIVEN SELECTION, Blood, 91(8), 1998, pp. 2948-2954
Citations number
39
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
91
Issue
8
Year of publication
1998
Pages
2948 - 2954
Database
ISI
SICI code
0006-4971(1998)91:8<2948:ETALUA>2.0.ZU;2-Y
Abstract
AL amyloidosis is characterized by fibrillar tissue deposits (amyloid) composed of monoclonal light chains secreted by small numbers of indo lent bone marrow plasma cells whose ontogenesis is unknown. To address this issue and to provide insights into the processes that accompanie d pathogenic light chain formation, we isolated the complete variable (V) regions of 14 light (VL) and 3 heavy (VH) chains secreted by amylo id clones at diagnosis (10 Bence Jones and 4 with complete Igs, 9 lamb da and 5 kappa) by using an inverse polymerase chain reaction-based ap proach free of primer-induced biases. Amyloid V regions were found to be highly mutated compared with the closest germline genes in the data bases or those isolated from the patients' DMA, and mutations were not associated with intraclonal diversification. Apparently high usage of the XIII family germline gene V lambda III.1 was observed (4 of 9 lam bda light chains), Analysis of the nature and distribution of somatic mutations in amyloid V regions showed that there was statistical evide nce of antigen selection in 8 of 14 clones (7 in VL and 1 in VH). Thes e results indicate that a substantial proportion of the amyloid clones developed from B cells selected for improved antigen binding properti es and that pathogenic light chains show evidence of this selection. ( C) 1998 by The American Society of Hematology.