Rearrangement and expression of rabbit immunoglobulin kappa light chain gene in transgenic mice.

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Abstract
To determine whether a foreign unrearranged immunoglobulin gene can be functionally rearranged and expressed in vivo, a rabbit b9 .kappa. light chain gene construct containing a single germ-line .kappa. chain variable (V) region gene (V.kappa.), the five .kappa. chain joining (J) segments (J.kappa.), and the .kappa. chain constant (C) region germ-line gene (C.kappa.) was introduced into fertilized mouse eggs. Eleven transgenic mice carrying 1-30 copies of the rabbit .kappa. gene construct were obtained. Rearrangement of the transgene due to V.kappa.-J.kappa. recombination was observed in the spleen of all the mice lines analyzed. Only the J.kappa.1 and J.kappa.2 segments, which have canonical sequences for rearrangement and high-level expression, are utilized in assembly of the rabbit gene. V.kappa.-J.kappa.1 and V.kappa.-J.kappa.2 joining was also observed in the thymus but not in nonlymphoic tissue. Polyadenylylated rabbit .kappa. chain transcripts of 1.2 kilobases were found in the spleen of the transgenic mice. the level of transcription was low despite a high level of rearrangement. Three transgenic mice lines secreted .kappa. light chains encoded by the foreign rabbit gene. Serum rabbit .kappa. chains were associated with mouse .mu. and .gamma.1 heavy chains. However, hybrid antibody molecules containing both rabbit and mouse .kappa. light chains were also found in the serum of these animals. These results suggest that, although the rabbit .kappa. chain gene construct contains the necessary sequences for gene assembly, sequences implicated in stage- and tissue-specific regulation of .kappa. chain gene rearrangement are either missing or not recognized by mouse lymphoid cells.