Antibody producing non-human animals
Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is human, human-like, or humanized. The nucleic acid is provided with a means that renders it resistant to DNA rearrangements and/or somatic hypermutations. In one embodiment, the nucleic acid comprises an expression cassette for the expression of a desired molecule in cells during a certain stage of development in cells developing into mature B cells. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.
1. A transgenic murine animal that has been immunized to generate an immune response against an antigen, wherein the genome of said animal comprises a transgene comprising a single human immunoglobulin light chain V gene segment fused to a single human immunoglobulin light chain J gene segment,
such that said fused V/J gene segments encode a rearranged immunoglobulin light chain variable region, wherein the transgene lacks a regulatory element that contributes to somatic hypermutation of the light chain variable region; and
said transgenic animal comprising a population of B cells that secrete a repertoire of antibodies that bind said antigen, said repertoire of antibodies comprising the immunoglobulin light chain variable region encoded by said transgene and a light chain constant region, paired with a diversity of immunoglobulin heavy chains resulting from somatic hypermutation in response to said antigen.
2. The transgenic animal of claim 1 , wherein the transgene comprises a murine light chain constant region gene segment.
3. The transgenic animal of claim 1 , wherein the animal is a mouse.
4. The transgenic animal of claim 1 , wherein said transgene comprises a human immunoglobulin light chain germline V gene segment fused to an immunoglobulin light chain germline J gene segment.
5. The transgenic animal of claim 1 , wherein said transgene lacks the intronic light chain enhancer MoEκi or comprises a truncation of the 3′ kappa enhancer, or a combination of the foregoing.
6. The transgenic animal of claim 1 , wherein the transgene comprises a human light chain constant region gene segment.