title: Antibody repertoires of four- and five-feature translocus mice carrying human immunoglobulin heavy chain and kappa and lambda light chain yeast artificial chromosomes.
abstract: We have produced mice that carry the human Ig heavy (IgH) and both kappa and lambda light chain transloci in a background in which the endogenous IgH and kappa loci have been inactivated. The B lymphocyte population in these translocus mice is restored to about one-third of normal levels, with preferential (3:1) expression of human lambda over human kappa. Human IgM is found in the serum at levels between 50 and 400 microg/ml and is elevated following immunization. This primary human Ab repertoire is sufficient to yield diverse Ag-specific responses as judged by analysis of mAbs. The use of DH and J segments is similar to that seen in human B cells, with an analogous pattern of N nucleotide insertion. Maturation of the response is accompanied by somatic hypermutation, which is particularly effective in the light chain transloci. These mice therefore allow the production of Ag-specific repertoires of both IgM,kappa and IgM,lambda Abs and should prove useful for the production of human mAbs for clinical use.
authors.affiliation: Laboratory of Developmental Immunology, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: I C
authors.initials: IC
authors.lastname: Nicholson
authors.forename: X
authors.initials: X
authors.lastname: Zou
authors.forename: A V
authors.initials: AV
authors.lastname: Popov
authors.forename: G P
authors.initials: GP
authors.lastname: Cook
authors.forename: E M
authors.initials: EM
authors.lastname: Corps
authors.forename: S
authors.initials: S
authors.lastname: Humphries
authors.forename: C
authors.initials: C
authors.lastname: Ayling
authors.forename: B
authors.initials: B
authors.lastname: Goyenechea
authors.forename: J
authors.initials: J
authors.lastname: Xian
authors.forename: M J
authors.initials: MJ
authors.lastname: Taussig
authors.forename: M S
authors.initials: MS
authors.lastname: Neuberger
authors.forename: M
authors.initials: M
authors.lastname: Brüggemann
mesh_terms: D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D001483:Base Sequence; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics* / Q000276:immunology; D003433:Crosses, Genetic; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006801:Humans; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000097:blood / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D011947:Receptors, Antigen, B-Cell