The incidence of allergic diseases has been steadily increasing in modernized societies and represents a
major public health problem. One of the main triggers of allergic responses is mediated by IgE antibodies
specific for allergen components. These IgE antibodies are secreted by terminally differentiated IgE plasma
cells, which are derived from B cells that have undergone class switch recombination to IgE. Recent
technological advances have enabled the direct study of IgE-expressing B cells in mice and humans. A
prevailing paradigm is that class switch recombination to IgE occurs in the context of type 2 immune
responses, such as allergic disease models and parasitic infection, whereas class switch recombination to IgE
is disfavored under type 1 immune responses to viruses and bacteria. We have found, however, that IgE class
switch recombination is broadly restrained under most types of immune responses by the cytokine IL-21,
acting through the IL-21 receptor and STAT3 in B cells. The overall objective of this study is to determine the
molecular basis by which the IL-21-STAT3 axis negatively regulates IgE class switch recombination. The
specific goals of this study are to: 1) characterize the molecular mechanism by which IL-21 regulates IgE class
switch recombination and 2) identify new genes involved in the regulation of IgE class switch recombination.
The results from these studies will help us understand how the initial class switch to IgE is regulated, thereby
giving us insights into how allergic sensitization occurs at a molecular level.