Unique Maturation Program of the IgE Response In Vivo

SummaryA key event in the pathogenesis of asthma and allergies is the production of IgE antibodies. We show here that IgE+ cells were exceptional because they were largely found outside germinal centers and expressed, from very early on, a genetic program of plasma cells. In spite of their extragerminal center localization, IgE+ cells showed signs of somatic hypermutation and affinity maturation. We demonstrated that high-affinity IgE+ cells could be generated through a unique differentiation program that involved two phases: a pre-IgE phase in which somatic hypermutation and affinity maturation take place in IgG1+ cells, and a post-IgE-switching phase in which IgE cells differentiate swiftly into plasma cells. Our results have implications for the understanding of IgE memory responses in allergy