Transgenic animals bearing human Igλ light chain genes
The invention relates to transgenic animals bearing one or more human λ light chain loci. The invention also relates to methods and compositions for making transgenic animals that have incorporated human λ light chain loci. The invention further relates to methods of using and compositions derived from the transgenic animals that have incorporated human λ light chain loci.
1. A transgenic mouse whose genome comprises a substantially complete human λ light chain locus comprising V, J, and constant region genes, wherein the mouse comprises YAC yL.
2. The transgenic mouse according to claim 1 , wherein said mouse further comprises a human immunoglobulin heavy chain locus comprising V, D, J, and constant region genes or a portion thereof, a human immunoglobulin κ light chain locus comprising V, J, and constant region genes or a portion thereof or both said human immunoglobulin heavy chain locus or portion thereof and said human immunoglobulin κ light chain locus or portion thereof.
3. A transgenic mouse whose genome comprises:
a) a substantially inactivated endogenous heavy chain locus;
b) a substantially inactivated endogenous κ light chain locus;
c) a human heavy chain locus comprising V, D, J, and constant region genes;
d) a human κ light chain locus comprising V, J, and constant region genes; and
e) a substantially complete human λ light chain locus comprising V, J, and constant region genes,
wherein the mouse comprises YAC yL.
4. A method for producing a cell line that produces a human monoclonal antibody or a fragment thereof directed to an antigen, comprising:
a) immunizing the transgenic mouse of claim 2 or 3 with said antigen;
b) allowing said transgenic mouse to mount an immune response to said antigen;
c) isolating B lymphocytes from said transgenic mouse;
d) immortalizing said B lymphocytes;
e) creating individual monoclonal populations of said immortalized B-lymphocytes; and
f) screening said immortalized B lymphocytes to identify a cell line that produces an antibody directed to said antigen.
5. A cell line produced by the method according to claim 4 .
6. The transgenic mouse of claim 1 , comprising an active endogenous lambda light chain locus.
7. The transgenic mouse of claim 2 , wherein the human immunoglobulin heavy chain locus is introduced by a YAC.
8. The transgenic mouse of claim 3 , wherein the transgenic mouse expresses human Ig-kappa chains and human Ig-lambda chains in a ratio of 60:40.
9. A method for producing a B lymphocyte that produces a human monoclonal antibody or a fragment thereof directed to an antigen, comprising:
a) immunizing the transgenic mouse of claim 2 or 3 with said antigen;
b) allowing said transgenic mouse to mount an immune response to said antigen;
c) isolating B lymphocytes from said transgenic mouse; and
d) screening said B lymphocytes to identify a cell that produces an antibody directed to said antigen.