CNRS. France: Scientists from the CNRS, INSERM and Université de Limoges, working in the Laboratoire Contrôle de la Réponse Immune B et Lymphoproliférations (CNRS/Université de Limoges)1 have demonstrated that the production of type E immunoglobulins (IgE)2 by B lymphocytes induces a loss in their mobility and the initiation of cell death mechanisms.
These antibodies, present in small quantities, are the most powerful "weapons" in the immune system and can trigger extremely violent immune reactions or immediate allergies (asthma, urticaria, allergic shock) as soon as their levels rise, even slightly. These findings, published online in Cell reports on 12 February 2015, thus elucidate how our bodies restrict the production of IgE in order to prevent an allergic reaction.
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 us. 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, our bodies have thus 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 by committing a sort of “hara-kiri” which strongly
reduces IgE production and hence the triggering of allergies. The
scientists 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.