The findings, which were demonstrated in mice, highlight the unique properties of a subset of B cells that normally controls immune responses and limits autoimmunity, in which an organism mistakenly attacks its own healthy tissue. The work appears Oct. 14, 2012, in the journal Nature.
B cells are the component of the immune system that creates antibodies, which fight pathogens like bacteria and viruses. However, a small subset of B cells, called regulatory B cells, works to suppress immune responses. These B cells are characterized by a cell-signaling protein called interleukin-10 (IL-10), giving these regulatory B cells the name B10 cells.
While B10 cells are small in number, they are important for controlling inflammation and autoimmunity. B10 cells can also limit normal immune responses during infections, reducing inadvertent damage to healthy body tissue.
"Regulatory B cells are a fairly new finding that we're just beginning to understand," said Thomas F. Tedder, PhD, professor of immunology at Duke and study author. "B10 cells are important because they make sure an immune response doesn't get carried away, resulting in autoimmunity or pathology. This study shows for the first time that there is a highly controlled process that determines when and where these cells produce IL-10."
Tedder and his colleagues studied the process of IL-10 production in the B10 cells of mice. Creating IL-10 requires physical interactions between B10 cells and T cells, which play a role in turning on the immune system.
The researchers found that B10 cells only respond to very specific antigens. Recognizing these antigens drives the function of B10 cells, causing them to turn off certain T cells when they bind the same antigen to prevent them from harming healthy tissue.
With this understanding of B10 cells, researchers set out to learn whether B10 cells could be harnessed as a cellular therapy, given their ability to regulate immune responses and autoimmunity.
"Since B10 cells are extremely rare, it was important that we find a feasible solution to reproduce these cells outside the body to make them available," Tedder said.
The researchers learned that the B10 cells could be isolated from the body and would maintain their ability to regulate immune responses. Moreover, they could be reproduced in large numbers.
"Normal B cells usually die quickly when cultured, but we have learned how to expand their numbers by about 25,000-fold. However, the rare B10 cells in the cultures expand their numbers by four-million-fold, which is remarkable. Now, we can take the B10 cells from one mouse and increase them in culture over nine days to where we can effectively treat 8,000 mice with autoimmune disease," said Tedder.
When a small amount of B10 cells were introduced into mice with multiple sclerosis-like autoimmune disease, their symptoms were significantly reduced, essentially turning off the disease.
"B10 cells will only shut off what they are programmed to shut off. If you have rheumatoid arthritis, you would want cells that would only go after your rheumatoid arthritis," continued Tedder. "This research shows that we may have the potential to unharness regulatory cells, make millions of copies, and introduce them back into someone with autoimmune disease to shut down the disease. This may also treat transplanted organ rejection."
Additional research is needed to learn how to expand human B10 cells and determine how B10 cells behave in humans, building on the study's insights into the mechanisms behind their function and autoimmunity."Autoimmune diseases are very complicated, so creating a single therapy that allows us to go after multiple disease targets without causing immunosuppression has proven to be difficult." Tedder said. "Here, we're hoping to take what Mother Nature has already created, improve on it by expanding the cells outside of the body, and then put them back in to let Mother Nature go back to work."
The research was supported by grants from the National Institutes of Health (AI56363 and AI057157), the Lymphoma Research Foundation, and the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH.
Rachel Bloch | EurekAlert!
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences