Researchers map programmed cell death in immune cells to prevent allergy.

Immunity is based on cells, B lymphocytes, which carry or secrete antibacterial or antiviral weapons, the immunoglobulins (IgG, IgM, IgA, IgE) or antibodies. Although these weapons of immunity offer protection, they can also sometimes turn on the body itself. This is the case for the most effective of antibodies, IgE, where even infinitesimal traces (these IgE are 100,000 times less abundant than other antibodies) can trigger extremely violent allergic reactions.

The lymphocytes that produce IgM, IgG or IgA are numerous, easily identifiable and persistent (as memory cells). For hitherto unexplained reasons, the cells that produce IgE are rare and have thus been the subject of very little study. In order to understand the mechanisms controlling IgE, the scientists first of all used genetic engineering to force cells to produce these antibodies in large numbers.

They then succeeded in demonstrating two principal control mechanisms. They showed that as soon as a B lymphocyte carries an IgE on its membrane, it freezes, swells, loses its pseudopods and becomes incapable of moving, although lymphocytes are generally highly mobile. The scientists also revealed that the lymphocyte activates several mechanisms leading to apoptosis, or programed cell death. This self-destruction causes the rapid elimination of lymphocytes carrying IgE, while other cells in the immune system are able to survive for up to several years.

During evolution, the human body has developed several self-restriction mechanisms around one of their most powerful immune weapons, IgE. Because a cell carrying IgE can no longer move, it can only survive for a brief period, just long enough to play a short-lived protective role against parasites, toxins and poisons. It then self-destructs which strongly reduces IgE production and hence the triggering of allergies.

The team now wish to explore in more detail the different molecular pathways governing this self-restriction. Indeed, these may constitute numerous new therapeutic targets whose pharmacological activation could block allergies, or even permit the reduction of other pathological B lymphocytes, such as those involved in lymphomas.

Source:  Le Centre national de la recherche scientifique