The mechanism underlying the inverse proportion between serum IgE concentration and Stat3 transcriptional activity depends on Stat3 mutation type

•In Stat3 dominant-negative mice, IL-4/Stat6 signaling is indispensable for the increase of serum IgE concentration.•The increased serum IgE concentration was accompanied by reduced IL-4/Stat6 signaling and lessened IgE-producing B cells.•The IgE concentration in mice serum is inversely proportional to Stat3 transcriptional activity.•Both decreased and increased Stat3 transcriptional activity resulted in decreased IgE-producing B cells. Abnormalities in the IL-6/STAT3 signaling pathway can sometimes result in extremely high levels of IgE concentration in serum, however, the regulatory role of STAT3 in IgE production is elusive. We used several genetically modified mice with distinctive germline Stat3 transcriptional activity to assess the influence of Stat3 on the biochemical characteristics of IgE and found that the IgE concentration in serum is inversely proportional to Stat3 transcriptional activity. Intriguingly, the serum IgE concentration is directly proportional to IgE-producing B cells in Stat3-GOF mice but inversely proportional in mice carrying Stat3 mutations with reduced transcriptional activity. For reduced Stat3 transcriptional activity induced high levels of IgE in the mice, IL-4/Stat6 signaling is indispensable for IgE production, but it was observed that an increased IgE concentration was accompanied by reduced IL-4/Stat6 signaling and lessened IgE-producing B cells, which implies that an increase in IgE concentration may result from an extended half-life of IgE but not an increasing number of IgE-producing cells.