A new study in mice where researchers replicated a rare type of immune cell in the lab and then infused it back into the body, is raising hope for a new treatment for severe autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.
The researchers, from Duke University Medical Center in the US, write about their work on a type of B cell, in a paper that was published online in Nature at the weekend.
B cells are immune cells that create antibodies to attack unwanted pathogens like bacteria and viruses.
The type that the researchers on this study focused on are known as regulatory B cells or B10, after interleukin-10 (IL-10), a cell-signalling protein that the cells use.
B10 cells help control immune response and limit autoimmunity, which is where the immune system attacks the body’s own healthy tissue as if it were an unwanted pathogen.
Although there aren’t many of them, B10 cells play a key role in controlling inflammation: they limit normal immune response during inflammation, thus averting damage to healthy tissue.
Study author Thomas F. Tedder is a professor of immunology at Duke. He says in a statement that we are only just beginning to understand these recently discovered B10 cells.
He says these regulatory B 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,” he adds.
For their study, Tedder and colleagues used mice to study how B10 cells produce IL-10. For IL-10 production to start, the B10 cells have to interact with T cells, which are involved in switching on the immune system.
They found B10 cells only react to certain antigens. They found that binding to these antigens makes the B10 cells turn off some of the T cells (when they come across the same antigen). This stops the immune system from harming healthy tissue.
This was a new insight into the function of B10 cells that spurred the researchers to see if they could take this further: what if it were possible to use this cellular control mechanism to regulate immune responses, particularly in respect of autoimmunity?
B10 cells however are not common, they are extremely rare. So Tedder and colleagues had to find a way to make a ready supply of them outside the body.
They found a way to isolate the B10 cells without damaging their ability to control the immune responses. And they found a way to replicate them in large numbers, as Tedder explains:
“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,” he adds.
The next stage was to try out the new B10 cells: could they influence autoimmunity sufficiently to affect disease symptoms?
They found when they introduced a small number of B10 cells into mice bred to have a disease similar to multiple sclerosis, their symptoms lessened significantly.
“B10 cells will only shut off what they are programmed to shut off,” explains Tedder.
If you have rheumatoid arthritis, you would want cells that would only go after your rheumatoid arthritis,” he adds.
He and his colleagues suggest their work shows there is potential to remove regulatory cells, replicate them in their millions, and put them back in the body of a person with an autoimmune disease and it will effectively “shut down the disease”, as Tedder describes it:
“This may also treat transplanted organ rejection,” he adds.
The researchers call for more studies to learn how to replicate human B10 cells, and find out how they behave in humans.
Autoimmune diseases are complex, so making a single therapy that targets several diseases without causing immunosuppression is not easy, Tedder explains.
“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,” he says.
Grants from the National Institutes of Health, the Lymphoma Research Foundation, and the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH, helped pay for the study.
Written by Catharine Paddock PhD