Murine expression of human IgA Lambda locus

Abstract

In humans, approximately 60% of expressed immunoglobulin light chains are of the Kappa type and 40% of the Lambda type. In mice, there is almost no expression from the Lambda locus and over 95% of light chains are of Kappa type. The present invention discloses, among other things, transgenic mice carrying most of the human Ig Lambda light chain locus in their genome. The resulting mice express light chains with Kappa/Lambda ratio similar to the human ratio. Breeding of HuIg Lamda mice to Kappa-deficient mice also is described, as well as the generation of human monoclonal antibodies from transgenic mice with human Ig Lambda locus.

1 - 34  (Canceled)  
     
     
         35 . A transgenic mouse comprising as a translocus a yeast artificial chromosome (YAC) of about 410 Kb, wherein the YAC contains at least a majority of the human Vλ genes of cluster A and all the human Jλ-Cλ segments in germline configuration, wherein the translocus shows high expression, and is able to compete equally with the endogenous mouse κ locus.  
     
     
         36 . A transgenic mouse comprising as a translocus a yeast artificial chromosome (YAC) of about 410 Kb, wherein the YAC contains at least a majority of the human Vλ genes of cluster A and all the human Jλ-Cλ segments in germline configuration, wherein the mouse has one or both endogenous Igκ alleles disrupted, and wherein the translocus shows high expression.  
     
     
         37 . A transgenic mouse comprising a 380 Kb region of the human immunoglobulin (Ig) λ light (L) chain locus in germline configuration, wherein the 380 Kb region resides on a yeast artificial chromosome (YAC) that accommodates the most proximal V (variable gene) λ cluster, wherein the 380 Kb region has 15 Vλ genes and all Jλ-Cλ segments with the 3′ region, wherein the 3′ region includes a downstream enhancer.  
     
     
         38 . The transgenic mouse according to  claim 35 , wherein the mouse includes a HuIgλ YAC that accommodates a 380 Kb region of the human λ light chain locus in authentic configuration with all Vλ genes of cluster A, the Jλ-Cλ segments and the 3′ enhancer.