DNA rearrangements in MPC-11 immunoglobulin heavy chain class-switch variants.

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Abstract
Ig H chain class switching has been observed in vitro. In the IgG2b-producing MPC-11 mouse myeloma cell line, IgG2a-producing cells arise at a high frequency. In some cases, switch variants producing normal-sized (MW 55,000) .gamma.2a H chains have arisen spontaneously from a mutagen-induced intermediate (ICR 9.7.1) that produces an unusually large (MW 75,000) H chain. Other switch variants were isolated directly from the parent cell line. The expressed and unexpressed .gamma.2b genes of MPC-11 can be distinguished in restriction endonuclease digests of total genomic DNA so that DNA rearrangements detected in MPC-11 variants can be directly associated with one or the other of these two genes. DNA rearrangements occurring on the expressed H chain chromosome of several MPC-11 .gamma.2a switch variants and on the expressed chromosome of the ICR 9.7.1 intermediate are described. All of these variants apparently express the parental H chain variable region (VH) gene, supporting previous protein studies. Mapping data are provided for the expressed gene of ICR 9.7.1 and one of the IgG2a-producing variant cell lines (ICR 9.9.2.1) derived from it. Advantages of an in vitro switching system for examining the dynamics of the Ig H chain class switch are discussed.