A team of scientists at the Garvan Institute of Medical Research, Australia, has identified a new anatomical structure within the human immune system. The discovery, reported in the journal Nature Communications, is an important step towards understanding how to make better vaccines.
Immune cells gather at the SPF. The purple band represents the surface of the SPF. Image credit: Imogen Moran / Tri Giang Phan.
The new anatomical structure was only discovered when Dr. Tri Giang Phan and colleagues made ‘movies’ of the immune system in action, using sophisticated high resolution 3D microscopy in living animals.
Jam-packed with immune cells of many kinds, the structure is strategically positioned to detect infection early, making it a one-stop shop for fighting a ‘remembered’ infection.
“It’s a remarkable reminder that there are still mysteries hidden within the body — even though scientists have been looking at the body’s tissues through the microscope for over three centuries,” Dr. Phan said.
In a study performed in mice, Dr. Phan and co-authors revealed the existence of thin, flattened structures extending over the surface of lymph nodes.
“These dynamic structures are not always present: instead, they appear only when needed to fight an infection against which the animal has previously been exposed,” they said.
The researchers also saw the structures — which they have named the subcapsular proliferative foci (SPFs) — inside sections of lymph nodes from patients, suggesting that they help fight reinfection in people as well as in mice.
Using sophisticated ‘two-photon’ in vivo microscopy, they could see that several classes of immune cells gathered together in SPFs.
Memory B cells, which carry information about how best to attack the infection, clustered there. So did other cell types that act as helpers.
Importantly, the scientists could also see that memory B cells were changing into infection-fighting plasma cells.
This is a key step in the fight against infection, because plasma cells make antibodies to recognize and fend off the invader and protect the body from disease.
“It was exciting to see the memory B cells being activated and clustering in this new structure that had never been seen before. We could see them moving around, interacting with all these other immune cells and turning into plasma cells before our eyes,” said Dr. Imogen Moran, first author of the study.
“SPF structures are perfectly placed to fight infection fast — so they can stop disease in its tracks before it takes hold,” Dr. Phan said.
“When you’re fighting bacteria that can double in number every 20 to 30 minutes, every moment matters. To put it bluntly, if your immune system takes too long to assemble the tools to fight the infection, you die. This is why vaccines are so important. Vaccination trains the immune system, so that it can make antibodies very rapidly when an infection reappears. Until now we didn’t know how and where this happened.”
“Now, we’ve shown that memory B cells rapidly turn into large numbers of plasma cells in the SPF. The SPF is located strategically where bacteria would re-enter the body and it has all the ingredients assembled in one place to make antibodies — so it’s remarkably well engineered to fight reinfection fast.”
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Imogen Moran et al. 2018. Memory B cells are reactivated in subcapsular proliferative foci of lymph nodes. Nature Communications 9, article number: 3372; doi: 10.1038/s41467-018-05772-7
