Some food allergies last a lifetime—and the reason might have to do with a particular type of antibody-producing immune cells identified in the blood of children with allergies to peanuts, according to a new study published in Science Translational Medicine. These findings may also apply to allergies to other kinds of foods. Around 6% of people in the United States are allergic to at least one type of food. The consequence of being allergic to things like peanuts or shellfish can range from slight discomfort to anaphylactic shock, and even death. Allergies are most common in infants and children and tend to become less intense—or even vanish—as people grow up. But not everyone is so lucky—and why some people stay allergic while others don't remains an open question. Identifying what is causing allergies to last so long could help treat them on a more long-term basis.Kenneth Hoehn, PhD One conundrum is that the cells that produce the antibodies usually associated with food allergies appear to be short-lived, while allergies are often lifelong. Now, a study co-authored by Kenneth Hoehn, PhD, who worked on the project when he was a member of the Kleinstein lab at Yale School of Medicine, shows that a particular subset of immune cells which produce the antibody type IgG could explain why peanut allergies persist in some children. Hoehn is now an assistant professor of biomedical data science at the Geisel School of Medicine at Dartmouth. The study’s senior author was Maria Lafaille, PhD, professor of pediatrics, immunology, and immunotherapy at the Icahn School of Medicine at Mount Sinai. Miyo Ota, PhD, and Weslley Fernandes-Braga, PhD, also at Mount Sinai at the time of the research, were additional first authors. Memory of an allergen Allergic reactions to food are largely caused by a group of antibodies called IgE. These proteins attach to mast cells—which are like large containers filled with histamines and other immune-reactive compounds. When something like a peanut particle attaches to an IgE that binds to peanuts, the antibody causes the mast cell to release these compounds into the bloodstream, setting off the biological response we would recognize as an allergic reaction. “IgE is a key step in causing allergies,” says Hoehn. And that’s where things start getting complicated. IgE and other antibodies are produced by a type of immune cell called a B cell. The "memory" subtype of these cells helps the immune system recall past threats—like old allergens or past infections—for future needs. But memory B cells that make IgE are “very rare—which seems odd given the fact that some people have allergies their whole lives,” he says. In 2019, Hoehn saw Lafaille give a talk at Yale about the mystery of the missing IgE-producing B cells. Lafaille’s work showed that rodents might store allergen information in a different type of B cell, one that produces an antibody type called IgG. IgGs usually target viruses and bacteria. But Lafaille posited that, when triggered, certain B cells that produce IgGs can transform into cells that produce IgE antibodies. Hoehn asked Lafaille about potential collaborations, and she brought him into this project. To test whether B cells that make IgGs could be storing allergen information in people, Lafaille and her colleagues compared blood samples from a cohort of 58 children with peanut allergies to those of 13 children without peanut allergies. The team found that kids with peanut allergies had a higher number of memory B cells marked with CD23, a protein found on the surface of some B cells that also make IgG. How many CD23 B cells children had was directly proportional to the level of peanut-reactive IgE in their blood. Building on this, Hoehn investigated the other genes expressed in the CD23 B cells of a subset of the children and found that a number of immune-related genes were active in the cells of children with peanut allergies. Training the immune system One important observation was that the researchers could compel IgG-producing cells taken from children with peanut allergies to make IgE in the lab. Together, the findings suggest that the CD23 expressing IgG memory B cells are “primed to switch to IgE,” says Hoehn. Together, these findings suggest that targeting this population of CD23 expressing IgG B memory cells could result in more long-lasting treatment of allergies. Those who develop CD23 IgG memory B cells primed to respond to certain allergens might be more likely to hold on to their food allergies later in life. The discovery comes along with other research published in the same issue of Science Translational Medicine showing that CD23 expressing IgG memory B cells have a similar response to other allergens, such as pollen from birch trees. Treatments for allergies—such as antihistamines and life-saving epinephrine—do exist. However, these therapies largely treat symptoms rather than underlying conditions. With some research suggesting that food allergies are becoming more common among both children and adults, “identifying what is causing allergies to last so long could help treat them on a more long-term basis,” says Hoehn.