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Titolo:
REPERTOIRE CLONING OF LUPUS ANTI-DNA AUTOANTIBODIES
Autore:
ROBEN P; BARBAS SM; SANDOVAL L; LECERF JM; STOLLAR BD; SOLOMON A; SILVERMAN GJ;
Indirizzi:
UNIV CALIF SAN DIEGO,DEPT MED 0663,SAM & ROSE STEIN INST RES AGING,9500 GILMAN DR LA JOLLA CA 92093 UNIV CALIF SAN DIEGO,DEPT MED 0663,SAM & ROSE STEIN INST RES AGING LAJOLLA CA 92093 UNIV CALIF SAN DIEGO,DEPT MED,THEODORE GILDRED CANC CTR LA JOLLA CA 92093 SCRIPPS CLIN & RES INST,DEPT IMMUNOL LA JOLLA CA 92037 TUFTS UNIV,DEPT BIOCHEM BOSTON MA 02111 UNIV TENNESSEE,MED CTR,HUMAN IMMUNOL & CANC PROGRAM KNOXVILLE TN 37920
Titolo Testata:
The Journal of clinical investigation
fascicolo: 12, volume: 98, anno: 1996,
pagine: 2827 - 2837
SICI:
0021-9738(1996)98:12<2827:RCOLAA>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN MONOCLONAL-ANTIBODIES; B-CELL REPERTOIRE; COMBINATORIAL LIBRARIES; AUTOIMMUNE RESPONSES; HIGH-AFFINITY; LPR MICE; VH-GENE; ERYTHEMATOSUS; IGM; EXPRESSION;
Keywords:
LUPUS; REPERTOIRE; AUTOANTIBODY; ANTI-DNA; PHAGE DISPLAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
64
Recensione:
Indirizzi per estratti:
Citazione:
P. Roben et al., "REPERTOIRE CLONING OF LUPUS ANTI-DNA AUTOANTIBODIES", The Journal of clinical investigation, 98(12), 1996, pp. 2827-2837

Abstract

To investigate the autoantibody repertoire associated with SLE, we have created phage display IgG Fab libraries from two clinically active SLE patients and from the healthy identical twin of one of these patients. The libraries from the lupus discordant twins were found to both include unusually large representations of the V(H)5 gene family. By panning with DNA, the SLE libraries each yielded IgG anti-doublestranded (ds) DNA autoantibodies, which are characteristic of lupus disease. These included a V(H)5 autoantibody from the affected twin, that has atargeted cluster of mutations that potentially improves binding affinity. The recovered IgG anti-dsDNA autoantibodies expressed the same idiotypes associated with the in vivo. IgG anti-dsDNA response of the respective SLE donor. Heavy-light chain shuffling experiments demonstrated a case in which the in vitro creation of anti-dsDNA binding activity required restrictive pairing of a heavy chain with V-lambda light chains similar to those in circulating anti-dsDNA autoantibodies. By contrast, IgG anti-ds autoantibodies could not be recovered from the library from the healthy twin, or from shuffled libraries with heavy chains from the healthy twin. These repertoire analyses illustrate how inheritance and somatic processes interplay to produce lupus-associated IgG autoantibodies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 22:13:02