A novel pathway that controls production of IgE in B cells

• Applicant: Professor Dr. Rolf Jessberger
• Subject Area: Immunology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 265594313

Allergies constitute a major human health problem. The incidence of allergies strongly increased over the past few decades, with now more than 10 % of the European population affected by allergies. Allergies are triggered by the immunoglobulin isotype E (IgE) produced by specifically activated B cells. IgE binds to mast cells, which release mediator compounds that cause the acute allergic reaction. Thus, the basic understanding of IgE production in B cells is key to eventually understanding allergies. We have identified a protein, SWAP-70, which regulates IgE production in B cells. In SWAP-70 deficient mice and in cultured, primary Swap-70-/- B cells, IgE production is reduced to about 10 % of wild-type levels. Our previous data showed SWAP-70 nuclear localization and its interaction with nuclear proteins. Our recent data show that SWAP-70 is involved in IL4 triggered nuclear processes specifically required for IgE production. Specifically, chromatin immunoprecipitation experiments suggest that SWAP-70 associates with a critical promotor region, Ie, which is essential for initiating the switch of B cells to generate IgE. Here, SWAP-70 controls the balance between STAT6, which supports Ie activation and thus IgE synthesis, and BCL6, which inhibits Ie activation. Our new hypothesis is that SWAP-70 supports IgE production through control of the STAT6-BCL6 antagonism. This proposal aims at elucidating the precise role of SWAP-70 in this nuclear process, its association with the Ie region, and its interactions with BCL6 and STAT6. Achieving these aims should allow us to define a new and important pathway of IgE production control in B cells with potential long-term medical implications with respect to allergies.

• DFG Programme: Research Grants