The human body has an incredibly efficient defense mechanism known as the immune system. It’s a complex network of cells, tissues and organs that tirelessly work to protect the body from external threats. Despite its effectiveness, the immune system is not perfect. Sometimes, it can mistakenly identify harmless substances like peanuts or flower pollen as enemies, triggering allergies. Scientists have extensively studied immune system failures, yet questions remain about the persistence of certain allergies. Two studies published in Science Translational Medicine on February 7 shed light on this mystery, finding that certain immune cells act as reservoirs of antibodies that trigger the body’s reaction to allergens.
Allergies are a defect of the immune system, according to Dr. Joan Bartra, who heads the pneumology and allergy department at Barcelona’s Hospital Clínic. The most common type is hypersensitivity allergy, mediated by IgE antibodies. These antibodies are produced by B lymphocytes to defend against allergens. When the body comes into contact with an allergen, the immune system is activated, producing symptoms of varying severity. This can range from mild urticaria (hives) to potentially fatal systemic allergic reactions like anaphylaxis. Studies indicate that approximately 10% of the world’s population suffers from allergies to environmental elements or foods.
For years, allergists have grappled with a perplexing question: why do certain allergies spontaneously disappear while others persist? “We know that IgE is produced through an immunological dialogue between different cells,” said Bartra. “B lymphocytes initiate the production of IgE and direct plasma cells (a type of B lymphocyte) to produce them in large quantities. However, plasma cells have limited memories and finite lifespans. So, if the allergen is not present, why do IgE-mediated allergies persist over time in most cases?”
Two groups of researchers set out to answer this question, and published their results simultaneously in Science Translational Medicine. Both found that a population of immune system cells, particularly memory B cells, may be responsible for allergic memory. “Allergen-specific IgE has a short half-life in humans — about 48 hours,” said Manel Jordana, a Spanish allergist at McMaster University (Canada) and co-author of one of the studies. “Previously, it was thought that long-lived plasma cells were responsible for consistently high IgE levels. However, recent research reveals that these IgE-producing plasma cells are actually short-lived. This suggests that the regeneration of IgE after allergen exposure occurs in other cells, particularly memory B cells.”
American researchers found that in a pediatric population with peanut allergies, the presence of these immune cells correlated with IgE concentrations. This indicates that these memory B cells play a role in the persistence of food allergies. Similarly, the McMaster University researchers found that this population of immune cells serves as a memory reservoir for IgE antibodies in patients with allergies and healthy individuals. “Our study found that allergen-specific memory B cells (MBC2) can become IgE-producing plasma cells upon re-exposure to the allergen. These cells may explain lifelong food allergies and serve as markers for clinical allergy development, indicating a predisposition to develop clinical allergies,” said Jordana.
New target for allergy treatments
Jordana explains that the two studies are not identical but complementary, and add credibility to the findings since two independent groups made the same key observation, offering a new target for allergy treatments. Disabling or eliminating the ability of these cells to produce IgE could greatly benefit patients with food allergies.
The findings point to new therapeutic targets, including drugs like dupilumab used for atopic dermatitis, which could potentially reduce the populations of these cells. “The discovery of MBC2 opens up exciting avenues for future research, as we still have many unanswered questions. For instance, we are currently focused on understanding the cellular and molecular signals that trigger the activation of MBC2 and their transformation into IgE-producing cells upon re-exposure to the allergen. We are also actively investigating the possibility of reprogramming MBC2 to produce harmless antibodies instead of IgE,” said Jordana.
According to Vicky Cardona, an allergist at Vall d’Hebron Hospital in Barcelona who was not involved in the research, these studies “significantly contribute to the understanding of how immune responses persist over time.” Ignacio Dávila (also not involved in the research), the president of the Spanish Society of Allergology, noted the high quality of the studies and their “potential impact on managing and potentially modifying IgE memory.” Bartra also acknowledged the clinical significance of the recent findings. “The studies have clinical implications that explain why immunotherapy is effective in the short term and why allergies can recur after months of tolerance. They challenge dogmas and offer new strategies for treating patients with persistent allergies.”
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