Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class switch recombination

Switch (S) regions are repetitive DNA sequences. During an immune response, one of several S regions recombine with a donor switch (Sμ) that is constitutively “on,” resulting in the production of antibodies with new functions. Donor Sμ is large and very repeat-rich, while another switch, Se, is less than half its size with a low density of repeats. We replaced Se with Sμ in mice. These mice switch to Se more effectively and produce high levels of IgE antibodies implicated in asthma, making this a useful model to study disease. In addition, placing Sμ outside of its native context revealed insights into how switches work.