When you fall ill or have an allergic reaction, special immune cells churn out antibodies to identify invaders such as bacteria (or allergens like pollen). Now, scientists at The Scripps Research Institute have figured out how some of those cells know what to do.
As described in a release today, the first time young B cells find pieces of an invader, perhaps bits of a virus or bacteria, they learn how to make antibodies. Some B cells turn into plasma B cells and manufacture antibodies immediately, slowly ratcheting up production over time. Others become memory B cells, which can remain dormant for years until a second infection triggers them to respond.
Those memory B cells fall into different classes. Immune cells called helper T cells secrete chemical signals that tell the B cells which class to choose. One of them, the IgG class, is populated by B cells that respond to most viruses and bacteria. IgA-class B cells are found in mucosal surfaces like the intestines. Cells in the IgE class respond to parasites like intestinal worms.
Exactly how the cells choose which class to join has been unclear. The Scripps researchers nailed down two specific molecules needed to change young, 'naive' B cells into IgG2a-class memory B cells. The proteins are called T-bet and RORα, according to a paper recently published in the advance online edition of Nature Immunology.
“This is a real breakthrough, in the sense that we now have a much better understanding of how B cell class is regulated, and how we might target that regulatory process in vaccine and drug design,” said lead author Michael McHeyzer-Williams, PhD, in the release.
The discovery could help researchers design more-effective vaccines. With the addition of a specific protein, the vaccine itself could encourage cells to fall in certain classes and induce long-term immunity. For example, the vaccine might include addition of T-bet and RORα, to help push more B-cells into the IgG2a class, which is effective against viruses. The same concept, reversed, could discourage memory B cells and reduce over-the-top immune reactions common in autoimmune, allergic and lymphoma conditions.
“Being able to target just that class of B cell would be an obvious advantage over existing therapies, such as steroids, that knock down large parts of the immune system," said McHeyzer-Williams.
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