Researchers have discovered a never-before-identified type of memory B cell, an immune cell that ‘remembers’ what a person is allergic to, potentially opening the door to new therapeutics to treat allergies, including life-threatening food allergies.
The immunoglobulin E (IgE) antibody is a key mediator of allergic responses in food allergies and allergic rhinitis, commonly known as hay fever. In someone with an allergy, the immune system overreacts, producing IgE that travels to cells to release chemicals that cause an allergic reaction. Each IgE is allergen-specific, which is why some people are allergic to cat hair and others to peanuts.
However, most of the body’s IgE-producing cells don’t live long, begging the question: How is the IgE-producing cell pool replenished? Researchers from McMaster University, Canada, in collaboration with the Danish pharmaceutical company ALK-Abelló A/S (ALK), may now have an answer: a never-before-identified type of immune cell that produces IgE antibodies.
“We’ve discovered a type of memory B cell that had unique characteristics and a unique gene signature that has not been described before,” said Josh Koenig, the study’s lead and co-corresponding author. “We found that allergic people had this memory B cell against their allergen, but non-allergic people had very few, if any.”
While B cells have very important functions, they’re notoriously hard to find. So, the researchers created tetramers, made up of four customized antigen molecules that tag specific B cells so they can be detected. The customization can cover everything from peanuts to COVID-19-specific B cells. In the current study, the researchers customized tetramers out of allergens that included birch allergy, house dust mite allergy, and peanut allergy to locate the elusive memory B cells, the cells responsible for ‘remembering’ antigens so the immune system can identify and fight them in future.
The researchers analyzed samples from ALK clinical trials of sublingual immunotherapies, using cutting-edge technology such as single-cell transcriptomics and deep sequencing of antibody gene repertoires to demonstrate a direct connection between IgE and a new type of memory B cell they called a type-2 memory B cell (MBC2).
“Even though allergies are the most prevalent disease worldwide, it is still not fully understood how allergy occurs and evolves into a lifelong condition,” said Peter Sejer Andersen, the study’s other corresponding author. “Finding the cells that hold IgE memory is a key step forward and a game-changer in our understanding of what causes allergy and how treatment, such as allergy immunotherapy, can modify the disease.”
The finding gives researchers a new target for allergy treatment, potentially leading to new therapeutics.
“The discovery really pinpoints two potential therapeutic approaches we might be able to take,” said co-author Kelly Bruton. “The first is targeting those MBC2s and eliminating them from an allergic person. The other option could involve changing their function and have them do something that’s not going to be ultimately harmful when the individual is exposed to the allergen.”
Further research is needed to better understand the mechanism of action of MBC2s and ultimately create therapeutics, but the discovery provides hope for allergy sufferers, particularly those with potentially deadly food allergies.
“These are the types of discoveries that you really need to make in order to develop the right therapeutics to block the right cells to stop the disease,” said Koenig.
Part of the funding for the research was provided by ALK-Abelló A/S.
The study was published in the journal Science Translational Medicine.
Source: McMaster University
