The present invention relates to transgenic non-human animals that are
engineered to contain human immunoglobulin gene loci. In particular,
animals in accordance with the invention possess human Ig loci that
include plural variable (V.sub.H and V.kappa.) gene regions.
Advantageously, the inclusion of plural variable region genes enhances
the specificity and diversity of human antibodies produced by the animal.
Further, the inclusion of such regions enhances and reconstitutes B-cell
development to the animals, such that the animals possess abundant mature
B-cells secreting extremely high affinity antibodies.