Upregulation of FcepsilonRI on human basophils by IgE antibody is mediated by interaction of IgE with FcepsilonRI

IgE is now known to upregulate the expression of FcepsilonRI on human basophils. It is not known which receptor on basophils mediates this process of upregulation.

We sought to determine whether galectin-3, FcepsilonRII (CD23), or FcepsilonRI were involved in the upregulation of FcepsilonRI by IgE.

The role of galectin-3 was examined by measuring the influence of alpha-lactose on upregulation. Basophils were examined for expression of FcepsilonRII (CD23) by flow cytometry and messenger (m)RNA expression. Functional discrimination between binding to FcepsilonRII or FcepsilonRI was examined through the use of mutant IgE-Fc fragments or anti-FcepsilonRII antibody.

Upregulation of FcepsilonRI on basophils in the presence of IgE was not altered by coincubation with alpha-lactose, eliminating a role for galectin-3. Basophils were not found to express FcepsilonRII, as determined by flow cytometry with enriched basophil preparations or RT-PCR with highly purified basophil preparations. A mutant of the Fc fragment of IgE (IgE-Fc), which binds to FcepsilonRI with a greater than 10-fold lower affinity than IgE or wild-type IgE-Fc but exhibits no change in affinity for FcepsilonRII, allowed us to distinguish between the functions of the two Fc receptors. The mutant (R334S; Henry et al 1997) was required at about 30-fold higher concentration than the wild-type IgE-Fc for the same stimulation of FcepsilonRI expression on basophils, thus excluding a role for FcepsilonRII in the response. In addition, treatment of basophils with anti-FcepsilonRII antibody (MHM6), which is known to be competitive with IgE, had no effect on the expression of FcepsilonRI or the ability of IgE to upregulate expression of FcepsilonRI.

Collectively, these data indicate that IgE interacts with FcepsilonRI to upregulate its expression on human basophils.