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Evidence that amyloidogenic light chains undergo antigen-driven selection.
Blood. 1998 Apr 15; 91(8):2948-54.Blood

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 lambda and 5 kappa) 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 lambdaIII family germline gene V lambdaIII.1 was observed (4 of 9 lambda 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.

Authors+Show Affiliations

Research Laboratories of Biotechnology and Organ Transplantation, Clinical Immunology Unit, Department of Internal Medicine, Pavia, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9531605

Citation

Perfetti, V, et al. "Evidence That Amyloidogenic Light Chains Undergo Antigen-driven Selection." Blood, vol. 91, no. 8, 1998, pp. 2948-54.
Perfetti V, Ubbiali P, Vignarelli MC, et al. Evidence that amyloidogenic light chains undergo antigen-driven selection. Blood. 1998;91(8):2948-54.
Perfetti, V., Ubbiali, P., Vignarelli, M. C., 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, 91(8), 2948-54.
Perfetti V, et al. Evidence That Amyloidogenic Light Chains Undergo Antigen-driven Selection. Blood. 1998 Apr 15;91(8):2948-54. PubMed PMID: 9531605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence that amyloidogenic light chains undergo antigen-driven selection. AU - Perfetti,V, AU - Ubbiali,P, AU - Vignarelli,M C, AU - Diegoli,M, AU - Fasani,R, AU - Stoppini,M, AU - Lisa,A, AU - Mangione,P, AU - Obici,L, AU - Arbustini,E, AU - Merlini,G, PY - 1998/5/16/pubmed PY - 1998/5/16/medline PY - 1998/5/16/entrez SP - 2948 EP - 54 JF - Blood JO - Blood VL - 91 IS - 8 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 lambda and 5 kappa) 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 lambdaIII family germline gene V lambdaIII.1 was observed (4 of 9 lambda 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. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/9531605/Evidence_that_amyloidogenic_light_chains_undergo_antigen_driven_selection_ L2 - https://medlineplus.gov/amyloidosis.html DB - PRIME DP - Unbound Medicine ER -