A yeast artificial chromosome (YAC) was constructed from human germline sequence of the immunoglobulin heavy chain gene cluster. This YAC consisted of 66 V-heavy gene segments, all 30 D gene segments, all 6 J segments, the C-mu, and the C-delta gene segments, the human gamma2 class switch recombination recognition site, followed by the gamma 1 constant region. Downstream of this, the human exons encoding the membrane sequence of gamma2 constant regions were introduced followed by a downstream murine enhancer element. Southern blot analysis confirmed that the YAC inserted into ES cells without any recombination events. Mice carrying this transgene in combination with other alleles are capable of producing high yields of human IgG1 to an immunized antigen.