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.