Gut-Derived Regulatory B Cells May Explain Efficacy of MS Immunotherapy
核心洞察
B-cell depletion therapies in MS may work not only by removing harmful B cells (搜索) but also by mobilizing protective regulatory B cells from the gut into the bloodstream and central nervous system.
Researchers analyzed immune cells from blood, cerebrospinal fluid, and intestinal mucosal tissue of MS patients and controls, revealing increased trafficking of beneficial gut-derived B cells (搜索) after treatment.
Higher levels of B cell-regulating factors were associated with better clinical outcomes in MS patients, according to the international research team led by Prof. Anne-Katrin Pröbstel.
An international research team has uncovered a previously unknown mechanism that may explain why B-cell depletion therapies are so effective in treating multiple sclerosis (搜索) (MS). The study, published in Science Translational Medicine, reveals that these therapies do more than simply eliminate disease-driving B cells (搜索) — they also appear to mobilize protective regulatory B cells that naturally reside in the gut, redirecting them into the bloodstream and central nervous system.
The research was led by Prof. Anne-Katrin Pröbstel, Managing Director of the Center for Neurology at the University Hospital Bonn (UKB), a member of the Cluster of Excellence ImmunoSensation3 at the University of Bonn, and research group leader at the German Center for Neurodegenerative Diseases (搜索) (DZNE). Collaborators included researchers from the Universities of Basel, Toronto, and Yale, as well as Université de Lausanne and UMC Amsterdam.
Dual Role of B Cells (搜索) in MS Pathogenesis
In multiple sclerosis (搜索), the most common chronic inflammatory disease of the central nervous system, B cells (搜索) mistakenly attack the myelin sheath — the protective covering surrounding nerves. This understanding has made B cells a key therapeutic target. However, researchers now recognize that not all B cells are harmful. Alongside disease-causing B cells, there exist beneficial B cells that help regulate immune responses and may positively influence disease course.
The study set out to investigate how B-cell depletion therapies affect these protective B-cell populations. First authors Dr. Tradite Neziraj and Dr. Elisabeth Pössnecker collected and analyzed immune cells from blood, cerebrospinal fluid, and intestinal mucosal tissue of both control subjects and B-cell-depleted MS patients, examining the cells for type and function.
Mobilizing the Gut-Immune Axis
The team observed that B-cell depletion therapy (搜索) promoted the trafficking of beneficial B cells (搜索) from the gut into the bloodstream and the central nervous system of people with MS.
"Our research shows that B cell depletion changes the levels of factors that regulate B cells (搜索) and is associated with an increased migration of protective gut-derived B cells," explained Prof. Pröbstel. "Interestingly, higher levels of these B cell-regulating factors were linked to better outcomes in patients with MS."
These findings suggest that the therapeutic benefit of B-cell depletion extends beyond the removal of harmful immune cells. The treatment appears to simultaneously recruit beneficial immune cells from the gut, adding a previously unrecognized dimension to its mechanism of action.
Implications for Future Therapies
The discovery opens new avenues for therapeutic development, raising the possibility of designing treatments that specifically harness beneficial gut immune cells — not only for MS but potentially for other inflammatory diseases as well. Rather than focusing solely on eliminating pathogenic cells, future strategies could aim to enhance the body's own regulatory immune compartments.
The study was supported by funding from the Swiss Multiple Sclerosis (搜索) Society, the Propatient Stiftung of the University Hospital of Basel, the Fondation Pierre Mercier pour la Science, the National Multiple Sclerosis Society, the Swiss National Science Foundation, the State Secretariat for Education, Research and Innovation under the European Union's Horizon 2020 program, and the German Research Foundation as part of Germany's Excellence Strategy. Dr. Neziraj received additional support through an Early Investigator Research Award from the U.S. Department of Defense's Multiple Sclerosis Research Program and a postdoctoral fellowship from the Swiss National Science Foundation.