Generation of binding molecules

A method for producing a population of antibodies which bind to a specific antigen, said method comprising:

• a) providing lymphoid tissue containing a population of B cells from a non-human transgenic animal immunized with said antigen;
• wherein said transgenic animal expresses a single rearranged human antibody light chain variable region (VL) from a VL nucleic acid,
• wherein said transgenic animal expresses a human antibody heavy chain variable region (VH) repertoire from a repertoire of VH nucleic acids,
• said B cell population expressing a repertoire of VHs and the single rearranged human antibody VL,
• said B cell population thus expressing a limited immunoglobulin light chain variable (VL) region repertoire,
• b) obtaining the nucleic acids encoding antibody heavy chain variable (VH) regions from said lymphoid tissue,
• c) obtaining nucleotide sequences of the obtained nucleic acids of step b),
• d) determining the frequency of nucleotide sequences from step c) which encode VH regions,
• e) providing host cells, wherein each host cell comprises at least one vector comprising a nucleotide sequence encoding at least one VH region selected from those in step d) wherein each said host cell expresses the single rearranged human VL nucleic acid of step a) and said at least one VH region selected in step d),
• f) culturing said host cells from step e and allowing for expression of said VL and VH regions, and
• g) obtaining said population of antibodies from the cultured host cells of step f) which bind said antigen,
• wherein the method is without performing hybridoma generation or use of display technology between steps b) and c).