High-avidity human IgG kappa monoclonal antibodies from a novel strain of minilocus transgenic mice.
Human immunoglobulin transgenic mice provide a method of obtaining human monoclonal antibodies (Mabs) using conventional hybridoma technology. We describe a novel strain of human immunoglobulin transgenic mice and the use of this strain to generate multiple high-avidity human sequence IgG kappa Mabs directed against a human antigen. The light chain transgene is derived in part from a yeast artificial chromosome clone that includes nearly half of the germline human V kappa region. In addition, the heavy-chain transgene encodes both human mu and human gamma 1 constant regions, the latter of which is expressed via intratransgene class switching. We have used these animals to isolate human IgG kappa Mabs that are specific for the human T-cell marker CD4, have high binding avidities, and are immunosuppressive in vitro. The human Mab-secreting hybridomas display properties similar to those of wild-type mice including stability, growth, and secretion levels. Mabs with four distinct specificities were derived from a single transgenic mouse, consistent with an extensive diversity in the primary repertoire encoded by the transgenes.
Fishwild
D M
DM
Department of Hybridoma Development, GenPharm International, Mountain View, CA 94043, USA. dfishwild@genpharm.com
O'Donnell
S L
SL
Bengoechea
T
T
Hudson
D V
DV
Harding
F
F
Bernhard
S L
SL
Jones
D
D
Kay
R M
RM
Higgins
K M
KM
Schramm
S R
SR
Lonberg
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000915:Antibody Affinity; D015704:CD4 Antigens / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006825:Hybridomas; D007074:Immunoglobulin G / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains