Immunization of hu-PBL–SCID mice and the rescue of human monoclonal Fab fragments through combinatorial libraries

ANTIBODIES are usually prepared from recently boosted animals and reflect ongoing immune responses 1–6 . In humans, this is restrictive as ethical constraints generally prevent antigen-boosting. Therefore the rich memory compartment of human antibody responses remains largely untapped 7 . Severe com...

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Veröffentlicht in:Nature (London) 1992-01, Vol.355 (6357), p.258-262
Hauptverfasser: Duchosal, Michel A., Eming, Sabine A., Fischer, Peter, Leturcq, Didier, Barbas, Carlos F., McConahey, Patricia J., Caothien, Roger H., Thornton, George B., Dixon, Frank J., Burton, Dennis R.
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container_end_page 262
container_issue 6357
container_start_page 258
container_title Nature (London)
container_volume 355
creator Duchosal, Michel A.
Eming, Sabine A.
Fischer, Peter
Leturcq, Didier
Barbas, Carlos F.
McConahey, Patricia J.
Caothien, Roger H.
Thornton, George B.
Dixon, Frank J.
Burton, Dennis R.
description ANTIBODIES are usually prepared from recently boosted animals and reflect ongoing immune responses 1–6 . In humans, this is restrictive as ethical constraints generally prevent antigen-boosting. Therefore the rich memory compartment of human antibody responses remains largely untapped 7 . Severe combined immune deficiency (SCID) mice 8 populated with human cells 9–11 allow the stimulation of human antibody memory without the usual constraints. Here we show how peripheral blood lymphocytes can be stimulated by antigen to produce large secondary responses after transfer to SCID mice. Specific monoclonal human Fab fragments can then be isolated from the mice by repertoire cloning even when the human donor's last contact with antigen was more than 17 years ago.
doi_str_mv 10.1038/355258a0
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Psychology ; Fundamental immunology ; Gene Library ; Hepatitis B Core Antigens - immunology ; Humanities and Social Sciences ; Humans ; Immunization ; Immunoglobulin Fab Fragments - immunology ; Immunoglobulin G - immunology ; Immunoglobulin Heavy Chains - immunology ; Immunoglobulin Light Chains ; Immunologic Memory ; letter ; Lymphocyte Transfusion ; Lymphocytes ; Lymphocytes - immunology ; Medical research ; Mice ; Mice, SCID ; Molecular immunology ; Molecular Sequence Data ; multidisciplinary ; Oligodeoxyribonucleotides ; Rodents ; Science ; Science (multidisciplinary) ; Techniques ; Transplantation, Heterologous</subject><ispartof>Nature (London), 1992-01, Vol.355 (6357), p.258-262</ispartof><rights>Springer Nature Limited 1992</rights><rights>1992 INIST-CNRS</rights><rights>Copyright Macmillan Journals Ltd. 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subjects Amino Acid Sequence
Animals
Antibodies, Monoclonal - immunology
Base Sequence
Biological and medical sciences
Blood
Cloning
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene Library
Hepatitis B Core Antigens - immunology
Humanities and Social Sciences
Humans
Immunization
Immunoglobulin Fab Fragments - immunology
Immunoglobulin G - immunology
Immunoglobulin Heavy Chains - immunology
Immunoglobulin Light Chains
Immunologic Memory
letter
Lymphocyte Transfusion
Lymphocytes
Lymphocytes - immunology
Medical research
Mice
Mice, SCID
Molecular immunology
Molecular Sequence Data
multidisciplinary
Oligodeoxyribonucleotides
Rodents
Science
Science (multidisciplinary)
Techniques
Transplantation, Heterologous
title Immunization of hu-PBL–SCID mice and the rescue of human monoclonal Fab fragments through combinatorial libraries
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