How to forget allergies

Good news!

"... a new study suggests a possible path towards one: getting the immune cells that produce problematic antibodies to forget what they were doing. ...

Researchers have now discovered that, in mice, if these B cells are exposed to their allergen in the absence of a key molecule called IL-4, they “forget” producing IgEs and make IgGs instead—a phenomenon known as class-switching—and they keep producing IgGs, even when IL-4 returns. ..."

From the Editor’s summary and abstract (a poorly written summary/abstract only for specialists):

"IgE antibodies in allergy are maintained by class switching of IgG1 memory B cells (MBCs) and IgE-fated type 2–polarized MBCs (MBC2s). Whether the type 2 phenotype of MBC2s and the IgE trajectory of allergen-specific MBCs are modifiable is unknown. Bruton et al. determined that IL-4 signaling maintained the MBC2 phenotype and controlled the IgE trajectory of MBCs. IL-4 blockade redirected the recall response to a type 1–like response, producing IgG2c antibodies. Exposure to type 1–polarizing adjuvants during the recall response reprogrammed MBCs generated in a type 2 environment to non-IgE fates, demonstrating the functional plasticity of MBCs. 

Abstract

Long-lived immunoglobulin E (IgE) responses against innocuous environmental and dietary antigens (Ags) are maintained by an IgG1-dominant memory B cell (MBC) compartment primed for interleukin-4 (IL-4) responsiveness. The plasticity of the MBC compartment destined for IgE class switch recombination remains poorly understood.

In this work, we report critical IL-4 and IL-13 dependency for the pathogenic IgE fate of type 2–polarized MBCs in allergy. Initiation of a recall response in the absence of IL-4 and IL-13 signaling diminished the type 2 MBC phenotype in mice and humans. This permitted the emergence of long-lived Ag-specific IgG2c+ MBCs in mice. The divergence to a type 1–like response was dependent on interferon-γ signaling and arose from both unswitched and class-switched Ag-specific B cells in vivo. This reprogrammed fate was sustained even beyond therapeutic intervention, revealing fundamental insights into the plasticity of the allergen-specific recall response."

ScienceAdviser

Pathogenic IgE-fated memory B cell responses retain functional plasticity (no public access)

Pathogenic IgE-fated B cell memory retains functional plasticity (preprint, open access, first published November 2023)