Chimaeric Surrogate Light Chains (SLC) Comprising Human VpreB

摘要

The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.

主权项

1. A non-human vertebrate or cell whose genome comprises an antibody heavy chain transgene, the transgene comprising
(a) one or more human VH gene segments, one or more human D gene segments and one or more human JH gene segments operably connected upstream of a constant region gene so that the transgene is capable of undergoing VDJ recombination in vivo to produce an antibody gene comprising a rearranged VDJC encoding an antibody heavy chain having a human variable region and a constant region; or (b) a rearranged VDJ encoding a human variable region operably connected upstream of a constant region gene so that the transgene encodes (optionally following VDJ combination with the constant region) an antibody heavy chain having a human variable region and a constant region; the genome further comprising
(i) a human VpreB gene capable of expressing a human VpreB, and(ii) a non-human vertebrate λ5 gene; wherein said vertebrate is optionally a mouse or rat, wherein the vertebrate or cell is capable of expressing a chimaeric surrogate light chain comprising human VpreB and non-human vertebrate λ5 for pairing with the heavy chain, and wherein said vertebrate cell is optionally a mouse or a rat cell.