Newfound immune cells are responsible for long-lasting allergies

Allergy sufferers may one day be able to erase the source of their congestion, itchy skin and swollen lips and throat thanks to two studies that have uncovered elusive immune cells that maintain allergies over the long haul, often for a lifetime.

A specialized type of immune cell called type 2 memory B cells or MBC2s hold the memory of proteins that cause allergies, two independent groups of researchers report February 7 in Science Translational Medicine. Memory B cells are important for long-lasting protection against infectious diseases, but this subset is primed to make the type of antibodies that lead to allergies.

Unmasking the cells’ identity might lead to new ways to diagnose, treat or even cure allergies.

In the United States, about a third of adults and a quarter of children have allergies, with symptoms ranging from seasonal sniffles to life-threatening reactions to food or insect stings. Allergies happen when the immune system unleashes a type of antibody called IgE on innocuous proteins. Usually, those antibodies are reserved for fighting parasitic worms, but in people with allergies, the antibodies target harmless things such as pollen, peanuts and pet dander (SN: 11/4/22).

While some allergies disappear over time or with therapy, others last a lifetime. For decades, scientists have been searching for the source of the long-lived allergies.

Recently, researchers found that cells that help the immune system remember vaccinations and natural infections may be involved. These memory B cells produce a different class of antibodies known as IgG, which ward off viral and bacterial infections and neutralize toxins. But no one had identified exactly which of those cells were recalling allergens or how they switched to making the IgE antibodies responsible for allergies.

To uncover the mysterious cells, two research teams took a deep dive into the immune cells of people with allergies and some without.

Immunologist Joshua Koenig and colleagues examined more than 90,000 memory B cells from six people with birch allergies, four people allergic to dust mites and five people with no allergies. Using a technique called RNA sequencing to find out what individual cells were making, the team identified specific memory B cells, that it dubbed MBC2s, that make antibodies and proteins associated with the immune response that fights parasitic worms and causes allergies.

In another experiment, Koenig and colleagues used a peanut protein to go fishing for memory B cells from people with peanut allergies. The team pulled out the same type of cells found in people with birch and dust mite allergies. In people with peanut allergies, those cells increased in number and produced IgE antibodies — the ones responsible for allergies — as the people started therapy to desensitize them to peanut allergens (SN: 9/4/19).

“That’s a smoking gun observation,” says Koenig, of McMaster University in Hamilton, Canada. “You find the cells present in the allergic people. It’s not present in the nonallergic people.… These cells are the ones that are making these antibodies, and that’s how this memory is being held.”

Another group led by Maria Curotto de Lafaille, an immunologist at the Icahn School of Medicine at Mount Sinai in New York City, also found that similar cells — which her group calls type 2 memory B cells — were more abundant in 58 children allergic to peanuts than in 13 kids without allergies.

It’s clear that both groups have found the same cells, says Cecilia Berin, an allergist and immunologist at Northwestern University Feinberg School of Medicine in Chicago. There are “very consistent findings between the two groups,” she says.

Lafaille’s team found that the cells are poised to switch from making protective IgG antibodies to allergy-causing IgE antibodies. Even before the switch, the cells were making RNA for IgE but didn’t produce the protein. Making that RNA enables the cells to switch the type of antibodies they make when they encounter the allergen. “They are one step ahead of other cells to respond and to switch,” she says.

The signal to switch partially depends on a protein called JAK, her group discovered. Stopping JAK from sending the signal could help prevent the memory cells from switching to IgE production, Lafaille says. Other researchers at Mount Sinai are testing a JAK inhibitor drug called abrocitinib in people with food allergies.  

Lafaille also predicts that allergists may be able examine aspects of these memory cells to forecast whether a patient’s allergy is likely to last or disappear with time or treatment.

Knowing which population of cells enshrines allergies in long-term memory may eventually help scientists identify other ways to starve or kill the allergy cells, Berin says. “You could potentially get rid of not only your peanut allergy but also all of your allergies.”