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

Abstract

Class switch of immunoglobulin from μ to γ occurs by recombination between two repetitive switch sequences: S_μ and S_γ. 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 J_H‐μ intron (defined as σ_μ) was inserted into the μ‐δ intron (defined as σ_μ) 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 σ_μ to σ_μ On the other hand, in a Burkitt lymphoma, Daudi, the DNA fragment from σ_μ to σ_μ was duplicated. These results suggest that homologous recombination between σ_μ and σ_μ sequences mediates class switch from μ to δ in human and that it occurs via unequal crossing‐over between sister chromatids or daughter chromosomes.