People with allergies may soon be able to alleviate their symptoms, like congestion or itchy skin, thanks to recent studies revealing that immune cells are responsible for allergies persisting long-term. Two independent research groups have identified a specialized type of immune cell known as type 2 memory B cells (MBC2s) as special cells that are able to hold the memories of proteins that cause allergies. These findings, reported on February 7 in Science Translational Medicine, open up new possibilities for targeting and limiting the effects of long-term allergies.
Approximately one-third of adults and one-quarter of children in the United States suffer from allergies, ranging from seasonal to severe reactions triggered by food or insect stings. Allergies occur when the immune system deploys antibodies, specifically IgE, against harmless proteins like pollen, peanuts, or pet dander. While some allergies may resolve over time or through therapy, others persist throughout a person’s life. The scientific community has been aiming to identify the source of these allergies for some time.
Recent research hinted at the involvement of cells responsible for immune system memory related to vaccinations and natural infections. Memory B cells are known to generate IgG antibodies, which are essential for combating viral and bacterial infections. However, two questions remained: which type of memory B cell could recall allergens, and how do they produce IgE antibodies, which are responsible for allergies?
Two research teams conducted in-depth analyses of immune cells from individuals with and without allergies to come to a conclusion. Immunologist Joshua Koenig and his team examined over 90,000 memory B cells from individuals with birch allergies, dust mite allergies, and those without allergies. Using RNA sequencing, they identified a specific memory B cell, known as MBC2s, which produces antibodies and proteins associated with allergy development.
In a separate experiment, Koenig’s team targeted memory B cells from individuals with peanut allergies using a peanut protein. Remarkably, the same MBC2 cells were isolated, and their numbers increased as therapy to desensitize individuals to peanut allergens progressed. It was this experiment that provided the final evidence to link the presence of MBC2 cells to the allergic response. As Koenig states, “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.”
A parallel study led by Maria Curotto de Lafaille at the Icahn School of Medicine at Mount Sinai in New York City further solidified these findings. Her team identified type 2 memory B cells, a comparable B cell population to MBC2, which were more abundant in children allergic to peanuts than in those without allergies.
Interestingly, both research groups observed that these memory cells have the ability to switch from producing protective IgG antibodies to allergy-inducing IgE antibodies. Lafaille’s team discovered that this transition is influenced by a protein called JAK. Inhibiting JAK’s signaling could potentially prevent the shift towards IgE production, offering a promising solution to long-term allergies. Researchers at Mount Sinai are actively testing a JAK inhibitor drug, abrocitinib, in individuals with food allergies.
Lafaille also believes that by examining these memory cells further, allergists may be able to better plan a course of action for their patients by determining whether allergies are likely to persist or diminish over time or with treatment. This understanding of the cells responsible for allergies in long-term memory cells could pave the way for more innovative strategies to neutralize these cells, offering a new way for people to be allergy-free.
