Our bodies rely on the production of potent, or 'high affinity', antibodies to fight infection. The process is very complex, yet Sydney scientists have discovered that it hinges on a single molecule, a growth factor, without which it cannot function.
There is much we do not yet understand about our immune system. In simple terms, our bodies produce B cells, which make antibodies, and T cells, which help them. Ways in which these cells operate and interact with each other are still coming to light.
Roughly eight years ago, a new subset of T cells, T follicular helper (TFH) cells, was identified. This important class of T cells operates in specific environments termed 'germinal centres', specialised areas within lymph organs where B cells proliferate to form high affinity antibodies whenever we fight infection. TFH cells play a critical role in that they communicate with, and help activate, B cells.
The novel finding made by Dr Cecile King and PhD student Alexis Vogelzang, from the Garvan Institute of Medical Research in Sydney, was that the molecule interleukin 21 (IL-21) is a growth factor for TFH cells. A paper detailing this finding was published online recently in the international journal Immunity.
A cytokine, or chemical messenger, IL-21 is already well known to immunologists. While its newly identified growth factor role is only one of several functions, that function is fundamental. Without IL-21, the all-important TFH cells could neither develop nor survive.
Dr Cecile King, head of the Mucosal Autoimmunity Group at Garvan, has been investigating the roles of IL-21 for several years. "We already knew that IL-21 was produced by TFH cells and that it was a major initiator of proliferation in B cells," she said. "We were surprised to find that TFH cells not only produce IL-21, they also absolutely need it to survive and they utilise it to function."
"We showed that if you take a mouse genetically deficient in IL-21 and immunise it, you don't get TFH cells and you don't get antibody production. Conversely, if you put IL-21 receptor sufficient, or normal, T cells into the same mouse, where of course the B cells remain abnormal, you recover the normal immune reaction."
"These specialised T cells are thought to be the ones that direct traffic. They are the only ones that can move into the B cell zone and initiate high affinity antibody production."
"Without IL-21, we probably wouldn't be completely immunodeficient, just severely compromised. In addition to the high affinity antibodies we're talking about, our bodies also produce a lot of low affinity antibodies for mopping up infection. That low level response happens around-the-clock and is one of our body's first lines of defence."
"You could say that IL-21 directs the most finely-tuned aspect of our immune response. The highly specialised weaponry developed on-the-spot to target aggressive invaders."
"This finding suggests novel ways to boost vaccination or natural defences."
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