Journal ArticleDOI
Human Antibodies from Transgenic Mice
Nils Lonberg,Dennis Huszar +1 more
TLDR
It is found that B cell development in these mutant mice can be rescued by the introduction of human germline-configuration heavy- and kappa light-chain minilocus transgenes, thus recapitulating both stages of the humoral immune response using human, rather than mouse, sequences.Abstract:
We have used homologous recombination in ES cells to engineer B cell-deficient mice that are incapable of expressing endogenous immunoglobulin heavy and kappa light chain genes. We find that B cell development in these mutant mice can be rescued by the introduction of human germline-configuration heavy- and kappa light-chain minilocus transgenes. The transgenes rearrange during B cell differentiation, and subsequently undergo class switching and somatic mutation in response to antigen stimulation; thus recapitulating both stages of the humoral immune response using human, rather than mouse, sequences. The mice can be immunized; and human sequence, antigen specific, monoclonal antibodies can be obtained using conventional rodent hybridoma technology. These animals are also of interest for studying the normal processes of immunoglobulin gene expression. We discuss the example of heavy chain class switching, which has not been previously observed within an autonomous transgene.read more
Citations
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Patent
Human antibodies derived from immunized xenomice
TL;DR: In this paper, a transgenic animal has been modified to produce antibodies in response to antigenic challenge, but whose endogenous loci have been disabled, and various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.
Patent
Transgenic mammals having human Ig loci including plural VH and VK regions and antibodies produced therefrom
TL;DR: In this paper, a transgenic non-human animal was engineered to contain human immunoglobulin gene loci, including plural variable (V H and Vκ) gene regions.
Journal ArticleDOI
Single domain camel antibodies: current status.
TL;DR: Because of their smaller size and the above properties, the VHH clearly offer added-value over conventional antibody fragments, they are expected to open perspectives as enzyme inhibitors and intrabodies, as modular building units for multivalent or multifunctional constructs, or as immuno-adsorbents and detection units in biosensors.
Journal ArticleDOI
High-avidity human IgG kappa monoclonal antibodies from a novel strain of minilocus transgenic mice.
Dianne M. Fishwild,Susan L. O'Donnell,Tasha Bengoechea,Debra Hudson,Fiona A. Harding,Susan L. Bernhard,Debbie Jones,Robert M. Kay,Kay M. Higgins,Stephen R. Schramm,Nils Lonberg +10 more
TL;DR: A novel strain of human immunoglobulin transgenic mice is described and the use of this strain to generate multiple high-avidity human sequence IgGκ Mabs directed against a human antigen is described.
Patent
Human ctla-4 antibodies and their uses
TL;DR: In this article, human sequence antibodies against human CTLA-4 and methods of treating human diseases, infections and other conditions using these antibodies were presented. But the method of using human sequence immunoglobulin was not considered.
References
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Journal ArticleDOI
RAG-1-deficient mice have no mature B and T lymphocytes
Peter Mombaerts,John Iacomini,Randall S. Johnson,Karl Herrup,Susumu Tonegawa,Virginia E. Papaioannou +5 more
TL;DR: The introduction of a mutation in RAG-1 into the germline of mice via gene targeting in embryonic stem cells is described and it is shown that this mutation either activates or catalyzes the V(D)J recombination reaction of immunoglobulin and T cell receptor genes.
Journal ArticleDOI
RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement
Yoichi Shinkai,Gary Rathbun,Kong-Peng Lam,E. M. Oltz,Valerie Stewart,Monica Mendelsohn,Jean Charron,Milton Datta,Faith Young,Alan M. Stall,Frederick W. Alt +10 more
TL;DR: Loss of RAG-2 function in vivo results in total inability to initiate V(D)J rearrangement, leading to a novel severe combined immune deficient (SCID) phenotype.
Journal ArticleDOI
Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production
TL;DR: Results indicate that BSF-1 and IFN-gamma as well as the T cells that produce them may act as reciprocal regulatory agents in the determination of Ig isotype responses.
Journal ArticleDOI
A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin μ chain gene
TL;DR: The importance of the membrane form of the μ chain in B-cell development is assessed by generating mice lacking this chain by disrupting one of the membranes exons of the gene encoding the μ-chain constant region by gene targeting in mouse embryonic stem cells.
Journal ArticleDOI
Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow.
TL;DR: Functional analysis demonstrates that the proliferative response to IL-7, an early B lineage growth factor, is restricted to S7+ stages and, furthermore, that an additional, cell contact-mediated signal is essential for survival of Fr.
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