Humanized immunoglobulin loci

Abstract

The present invention concerns methods and means to produce humanized antibodies from transgenic non-human animals. The invention specifically relates to novel immunoglobulin heavy and light chain constructs, recombination and transgenic vectors useful in making transgenic non-human animals expressing humanized antibodies, transgenic animals, and humanized immunoglobulin preparations.

What is claimed is: 
     
       1. A B cell from a transgenic rabbit, wherein said transgenic rabbit comprises a humanized immunoglobulin (Ig) locus comprising multiple Ig gene segments, present in a transgenic vector wherein:
 (a) at least one of said gene segments is a human Ig gene segment comprising two or more identical or different units consisting of, from 5′ to 3′ direction, a 5′ nucleotide sequence, a human immunoglobulin heavy or light chain V gene segment, and a 3′ nucleotide sequence, wherein said 5′ nucleotide sequence and said 3′ nucleotide sequence have the nucleotide sequence of SEQ ID NO: 35; 
 (b) said gene segments are juxtaposed in an unrearranged, partially rearranged or fully rearranged configuration, and 
 (c) said humanized Ig locus is capable of undergoing gene rearrangement, if necessary, and gene conversion and/or hypermutation, and producing a repertoire of humanized immunoglobulins in said transgenic rabbit. 
 
     
     
       2. The B cell of  claim 1 , wherein said transgenic rabbit preserves an essentially intact endogenous regulatory and antibody production machinery. 
     
     
       3. The B cell of  claim 1  or  claim 2 , wherein said human Ig heavy chain V gene segment is a member of the VH3, VH1, VH5, or VH4 family.