B cells are crucial for the proper functioning of the immune system. However, researchers at Karolinska Institutet have shown that they can sometimes do more harm than good, as their numbers rise sharply after damage to the intestines, preventing tissues from healing. The results presented in the journal immunitymay be important in the treatment of inflammatory bowel disease.
B cells are a type of white blood cell that play an important role in the immune system, in part by producing antibodies that attack bacteria and viruses. Previous research has shown that people with inflammatory bowel disease (IBD), such as Crohn’s disease or ulcerative colitis, have many more B cells in their gut than healthy people. It has therefore been suggested that B cells might influence the severity of these diseases. Researchers at the Karolinska Institutet in Sweden have now tried to find out whether, and if so how, B cells contribute to IBD.
Strong increase during healing
“We were able to show that the B cell population in the colon increases sharply during the healing of colon lesions and that these cells accumulate mainly in areas where the damage is severe,” says study leader Eduardo Villablanca, associate professor at the Faculty of Medicine (Solna), Karolinska Institutet. “This in turn prevents the interaction between two other cell types – stromal and epithelial cells – which is necessary for tissue healing.”
Researchers examined an experimental colitis model and tissues from patients with ulcerative colitis using a range of methods to analyze cell populations. In particular, they focused on how B cells affect healing in the gut lining and found that B cell-deficient mice recovered from gut damage much faster than normal mice. The finding that B cells appear to do more harm than good in intestinal inflammation may have implications for the treatment of IBD.
Drugs that affect B cells
“There are already approved drugs that affect B cell response that are used for other diseases,” says Gustavo Monasterio, a postdoc in Dr. Villablanca at Karolinska Institutet and one of the leading authors. “We now want to test whether the depletion of B cells at certain time windows could also work in IBD. We also need to find out whether the accumulation of B cells can have a long-term beneficial effect, for example by altering the composition of bacteria in the gastrointestinal tract.”
The study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow program), and the German Research Foundation DFG. Eduardo Villablanca has received research grants from pharmaceutical company F. Hoffmann-La Roche and co-author Camilla Engblom is a Scientific Advisor for biotech company 10X Genomics Inc. Julio Saez-Rodriguez has received funding from Glaxo Smith Kline and Sanofi and consulting fees from Travere Therapeutics.
Materials provided by Karolinska Institute. Note: Content can be edited for style and length.