B cells are critical to proper immune system functioning, but research headed by scientists at Karolinska Institutet has now found that B cells can sometimes do more harm than good. The team’s study in mouse models and tissue from human patients with colitis found that B cell numbers greatly increase after bowel damage, preventing the tissue from healing. The results could have significance for inflammatory bowel disease (IBD) therapeutic strategies.
“We’ve been able to show that the B cell population increases sharply in the colon during the healing of colonic lesions, and that these cells mainly accumulate in areas where the damage is severe,” said principal investigator Eduardo Villablanca, PhD, associate professor at the department of medicine (Solna), Karolinska Institutet. “This prevents, in turn, the interaction between two other cell types—stromal and epithelial cells—which is needed for the tissue to heal.”
Villablanca and colleagues reported on their findings in Immunity, in a paper titled, “B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing,” in which they concluded, “Overall, our data suggest that the modulation of B cell responses during intestinal tissue repair phase might pose an alternative therapeutic approach for IBD.”
B cells are a type of white blood cell that produces antibodies to attack invading bacteria and viruses. Previous research by the Karolinska Institutet team, and by other researchers, has shown that people with chronic inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis (UC) have many more B cells in their intestines than healthy individuals, and it has been proposed that B cells might affect the severity of these diseases. “Alterations in the number of plasma cells and local production of IgA in patients with IBD compared with healthy individuals was first reported two decades ago,” the team noted. “Accumulation of B cells in the inflamed intestine was further confirmed in IBD patients, as well as experimental models of colitis … we have previously observed an enriched B cell transcriptomic signature in patients with ulcerative colitis type 1 (UC1), which are refractory to biological therapies.”
The Karolinska Institutet investigators wanted to find out if—and if so how—B cells might contribute to IBD. “To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration,” they wrote. To do this the researchers studied an experimental mouse model of colitis, and tissue from patients with ulcerative colitis, using a range of methods to analyze cell populations. “… we longitudinally characterized immune cell populations in murine colonic tissue during the process of dextran sodium sulfate (DSS)-induced intestinal damage and mucosal healing (MH),” the team explained. “… we examined the impact of B cell accumulation using loss-of-function experiments with transcriptomic analysis at the single-cell and whole tissue level.”
Focusing particularly on how B cells affect healing in the intestinal mucosa, the team found that mice lacking B cells recovered much more quickly after bowel damage than regular mice. “By combining scRNA-seq, spatial transcriptomics (ST), spatial phenotyping, and organoid-fibroblast co-cultures, we determined that BCD [B cell depletion] leads to increased interactions between epithelial and stromal cells within the damaged area indicating a detrimental role for excessive B cell expansion during MH.”
The finding that the B cells seem to do more harm than good in colonic inflammation might be relevant to future strategies for treating IBD, they suggested. “Our results provide a causal explanation for the observation that B cells accumulated in UC patients and support the possibility that BCD might be beneficial for achieving remission.”
Gustavo Monasterio, PhD, who is part of Villablanca’s research group at Karolinska Institutet and one of the lead authors of the newly reported work, added, “There are already approved drugs that affect the B cell response and that are used for other diseases. We now want to test if depleting B cells at specific time windows could also work with IBD. We also need to find out if the accumulation of B cells can have a long-term beneficial effect, such as by changing the composition of bacteria in the gastrointestinal tract.”