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

Preceding antibody constant regions are switch (S) regions varying in length and repeat density that are targets of activation-induced cytidine deaminase. We asked how participating S regions influence each other to orchestrate rearrangements at the IgH locus by engineering mice in which the weakest S region, S epsilon, is replaced with prominent recombination hotspot S mu. These mice produce copious polyclonal IgE upon challenge, providing a platform to study IgE biology and therapeutic interventions. The insertion enhances epsilon germ-line transcript levels, shows a preference for direct vs. sequential switching, and reduces intraswitch recombination events at native S mu. These results suggest that the sufficiency of S mu to mediate IgH rearrangements may be influenced by context-dependent cues.