Study: Peanut-Specific IgE B Cells Reveal Their Mysteries
Last month, researchers at Stanford University published a study that shed new light on blood cells that play an essential role in peanut allergy. These very rare IgE B cells make peanut-specific IgE antibodies that, when bound to peanut protein, can trigger the release of histamines and other molecules that cause reaction symptoms.
B cells are a type of white blood cell that can bind to a foreign protein and secrete its own proteins, called antibodies, to target and attack the foreign protein, or antigen. Different types of B cells produce different types of antibodies, of which IgE are the least common. In a properly functioning immune system, IgE antibodies target antigens on invading parasites, such as disease-causing worms. When IgE antibodies bind to a normally harmless foreign protein and trigger a harmful immune response, the foreign protein is called an allergen, and the immune response is called an allergic reaction.
IgE B cells haven’t been well studied because they are so scarce. While a single drop of blood contains millions of cells, the researchers found only 89 IgE B cells total in six blood samples pooled together from peanut-allergic individuals. Advances in biology now allow researchers to sequence the gene transcripts in a single cell; these gene transcripts reveal which DNA sequences in the cell are being used to manufacture proteins, including antibodies. Using this sequencing method, investigators characterized the antibodies made by each of the 89 cells. The results of this analysis offer several new insights.
Most of the 89 IgE B cells could quickly churn out large volumes of IgE antibodies. Previous research has shown that IgE B cells typically inherit pre-formed antigen-binding proteins from other types of B cells; if the IgE B cells manufactured and fine-tuned their own antigen specificity, IgE antibody maturation would take more time. Both of these traits may help explain the speed with which allergic reactions can strike.
Some regions of an antibody gene are conserved, that is, similar across different antibodies, while other regions are highly variable, able to generate a wealth of different antibodies that can bind to countless antigens. Researchers were intrigued to find that antibodies from six of the isolated IgE B cells – three cells each from two of the six allergic individuals – had variable regions that were remarkably similar. These six antibodies were able to bind not just one, but several peanut allergens, and some of this binding was very strong and specific. It’s possible that these similar antibody segments may represent a successful defense, evolved more than once and handed down from parents to offspring, which helps promote binding to a range of invading pathogens and, unfortunately, also helps antibodies bind to peanut proteins.
Another instance of similarity in peanut-binding antibodies was between an IgE antibody and an IgG4 antibody from the same individual. Food-specific IgG4 antibodies are associated with food tolerance, and levels of food-specific IgG4 increase dramatically during food allergen immunotherapy. These food-specific IgG4 antibodies compete against IgE antibodies in binding food allergens.
Finally, researchers were able to engineer new antibody variants based on the IgE antibodies they isolated and sequenced. By making changes to the antibody sequences, the researchers were able to diminish binding of the engineered antibodies to peanut allergens. Both IgG4 antibodies and antibody engineering represent promising new avenues to explore in the search for food allergy therapies.