B cells regulate immune responses and can be altered to prevent Multiple Sclerosis symptoms

Recent research reveals that B cells, not just T cells, play a significant role in orchestrating immune responses by releasing specific cytokines. This challenges the long-held belief that T cells are the principal orchestrators in the immune system. In individuals with Multiple Sclerosis (MS), B cells show abnormally active respiration, prompting myeloid cells and T cells to initiate pro-inflammatory responses. These responses lead to attacks on the myelin sheath protecting nerve fibers, resulting in nerve damage and MS symptoms.

Traditionally, it was thought that T cells were the main drivers of immune responses and that MS was largely caused by overly reactive T cells. However, the new study led by the Perelman School of Medicine at the University of Pennsylvania indicates that the interaction among multiple cell types, particularly the modulation of myeloid cells by B cells, is more critical than previously understood. This finding underscores the complex nature of immune system regulation, where different cell types and their interactions play important roles.

The immune system constantly responds to various stimuli by either activating or suppressing immune responses through the release of cytokines. These cytokines direct other cell types on how to respond, maintaining a balance between attacking pathogens and protecting the body from overactive responses that can lead to autoimmune diseases like MS. The study used human samples and mouse models to demonstrate that cytokine signaling between B cells and T cells is disrupted in MS. Specifically, B cells in MS patients produce abnormal cytokines that drive myeloid cells to generate inflammatory responses.

Researchers identified that the root of this problem lies in a metabolic dysregulation within B cells, specifically in a process known as oxidative phosphorylation. This type of mitochondrial respiration enables normal B cells to break down oxygen and release chemical energy signals. These signals prompt further responses within the B cells and myeloid cells, dictating whether to produce pro- or anti-inflammatory responses. However, when B cell metabolism is overly active, as seen in MS, it results in abnormal signaling that causes both myeloid and T cells to react in ways that contribute to MS symptoms.

An exciting development in MS treatment is the potential use of Bruton's tyrosine kinase (BTK) inhibitors. These inhibitors can modulate the overactive respiration in B cells, potentially halting the cascade of immune cell interactions that lead to inflammation and MS activity. Unlike existing MS therapies such as anti-CD20 treatments that deplete B cells and compromise the immune system, BTK inhibitors correct the metabolic abnormalities in B cells without depleting them. This approach makes B cells less likely to initiate pro-inflammatory responses, offering a promising avenue for MS treatment.

The study received funding from several sources, including the Melissa and Paul Anderson Gift Fund, the National Institutes of Health Autoimmunity Center of Excellence, and the Children's Hospital of Philadelphia Center for Mitochondrial and Epigenomic Medicine. Additional support came from grants from the National Natural and Science Foundation of China and a sponsored research agreement between The University of Pennsylvania and Biogen.

This groundbreaking research highlights the importance of understanding the intricate interactions within the immune system and opens new possibilities for treating MS by targeting B cells' metabolic processes.