Class switch from μ to δ is mediated by homologous recombination between σμ and σμ sequences in human immunoglobulin gene loci

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Abstract
Class switch of immunoglobulin from μ to γ occurs by recombination between two repetitive switch sequences: Sμ and Sγ. However, there are no such sequences in the μ‐δ introns of human and mouse genomes. Although the frequency of IgD‐secreting cells is extremely low in mouse about 1% of patients with myeloma produce IgD in human. In a previous report (Nucleic Acids Res. 1988. 16: 9497) we reported that a 442‐bp DNA sequence located in the JH‐μ intron (defined as σμ) was inserted into the μ‐δ intron (defined as σμ) in the human genome. There is no such insertion in mouse. We analyzed Ig H chain gene loci of two human IgD myelomas: one was analyzed by cloning and sequencing and the other by Southern hybridization. We found that recombination had occurred between these two homologous DNA sequences, resulting in loss of the DNA segment from σμ to σμ On the other hand, in a Burkitt lymphoma, Daudi, the DNA fragment from σμ to σμ was duplicated. These results suggest that homologous recombination between σμ and σμ sequences mediates class switch from μ to δ in human and that it occurs via unequal crossing‐over between sister chromatids or daughter chromosomes.