Structure of a rearranged gamma 1 chain gene and its implication to immunoglobulin class-switch mechanism

An expressed gene for gamma 1 chain of MC 101 myeloma was cloned from a phage library containing partial EcoRI digests of MC 101 DNA. The cloned DNA was analyzed by restriction enzyme cleavage, Southern blot hybridization, R-loop formation, and nucleotide sequence determination. The results indicate that the expressed gamma 1 chain gene comprises at least four germline DNA segments, namely a variable-region gene, a segment of the 5' flanking region of the mu chain gene (containing J regions), a segment of the 5' flanking region of the alpha chain gene, and the gamma 1 chain gene with its flanking regions. The presence of the alpha chain gene-flanking switch (S) region (S alpha region) at the 5' side of the gamma 1 chain gene-flanking region (S gamma 1 region) indicates that the heavy chain class switch may not be mediated by stepwise linear deletion along the order of the heavy chain constant-region genes (5'-mu-gamma 3-gamma 1-gamma 2b-gamma 2a-alpha-3'). We propose a siter-chromatid exchange model that explains class switch-associated deletion of heavy chain genes by unequal crossing-over events between sister chromatids.