Antibody producing non-human animals

Abstract

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 process for producing a B cell that produces an antibody that binds to a desired antigen, wherein the process comprises isolating a B cell from a transgenic murine animal that has been immunized to generate an immune response against the antigen, wherein the genome of said animal comprises:
 (1) a transgene comprising a single human immunoglobulin light chain V gene segment fused to a single human immunoglobulin light chain J gene segment, which transgene encodes 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 wherein:
 (i) the transgene comprises a nucleic acid sequence encoding an immunoglobulin light chain constant region, or 
 (ii) the variable region of the transgene is operably linked to an endogenous immunoglobulin light chain constant region gene segment; and 
   (2) an immunoglobulin locus of a heavy chain, wherein the locus is capable of forming a diversity of heavy chain variable regions.   
     
     
         2 . The process of  claim 1 , wherein the transgenic animal is a mouse. 
     
     
         3 . The process of  claim 1 , wherein the transgene comprises a nucleic acid sequence encoding a murine light chain constant region. 
     
     
         4 . The process of  claim 1 , wherein the transgene comprises a nucleic acid sequence encoding a human light chain constant region. 
     
     
         5 . The process of  claim 2 , wherein the variable region of the transgene is operably linked to an endogenous immunoglobulin light chain constant region gene segment.