Cloning of human immunoglobulin epsilon chain genes: evidence for multiple C epsilon genes.

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Abstract
An active human epsilon chain gene was cloned from a phage library containing partial EcoRI digests of IgE-producing myeloma DNA, using the human JH (joining) gene fragment as a probe. The epsilon chain gene clone was identified by partial nucleotide sequence determination. The germ-line constant region gene of the epsilon chain (C epsilon gene) was cloned from a human fetal liver DNA library, using the cloned epsilon chain gene as a probe. Comparative studies on the human and mouse germ-line epsilon chain genes revealed that the switch (S) sequence is more conserved than the coding sequence. Restriction endonuclease BamHI digestion of human DNA produced three C epsilon fragments of 3.0, 6.5, and 9.2 kilobases, which were named C epsilon 1, C epsilon 2, and C epsilon 3 genes, respectively. We found the three C epsilon gene fragments in all of the human DNA preparations from eleven individuals. The C epsilon gene expressed in the myeloma was identified as the C epsilon 1 gene. Because the C epsilon 2 gene is deleted from the myeloma DNA, the order of the C epsilon genes is likely to be 5'-C epsilon 2-C epsilon 1-C epsilon 3-3', assuming that all the C epsilon genes are on chromosome 14. The germ-line C epsilon 3 gene was also cloned from the myeloma DNA. Characterization of the C epsilon 3 gene revealed that it does not have the S region, suggesting that it might be a pseudogene.