B cells have been found to control responses of myeloid cells through the release of specific cytokines, challenging the long-held belief that T cells are solely responsible for orchestrating immune responses. Research conducted by the Perelman School of Medicine at the University of Pennsylvania has revealed that individuals with Multiple Sclerosis (MS) exhibit abnormally active respiration in B cells, leading to pro-inflammatory responses by myeloid cells and T cells. This abnormal immune response results in the attack on the protective sheath covering nerve fibers, causing nerve damage and the symptoms associated with MS.
A novel class of drugs known as Bruton’s tyrosine kinase (BTK) inhibitors has shown promise in altering the abnormal respiration in B cells, potentially halting the signaling that leads to MS flare-ups. The study, led by Dr. Amit Bar-Or, Director of Penn’s Center for Neuroinflammation and Neurotherapeutics, challenges the conventional understanding that T cells are the main drivers of immune responses. The research emphasizes the importance of interactions between multiple cell types in the immune system, with B cells playing a more significant role in modulating myeloid cells than previously thought.
A key aspect of maintaining a balanced immune response involves the release of different cytokines that instruct various cell types on how to respond to stimuli. In the case of MS, researchers discovered that cytokine signaling between B cells and T cells is disrupted, leading to the abnormal production of cytokines by B cells in MS patients. This aberrant cytokine profile drives myeloid cells to generate an inflammatory response, contributing to the progression of MS symptoms.
Metabolic dysregulation in B cells, specifically within the process of oxidative phosphorylation, was identified as a crucial factor in driving the abnormal immune responses observed in MS. In normal circumstances, B cells can regulate immune responses by releasing chemical signals produced through oxygen breakdown. However, in individuals with MS, overactive B cell metabolism leads to abnormal signaling that triggers pro-inflammatory responses in myeloid and T cells, exacerbating MS symptoms.
One potential therapeutic approach identified in the study involves targeting the overactive respiration in B cells using BTK inhibitors. These drugs have been shown to reduce the metabolic abnormalities in B cells of MS patients, preventing the release of abnormal cytokines that drive inflammatory responses in myeloid cells and T cells. Unlike existing MS therapies that deplete B cells, BTK inhibitors correct the metabolic dysregulation without compromising the individual’s overall immune response.
The research, funded by various sources including the Melissa and Paul Anderson Gift Fund and the National Institutes of Health Autoimmunity Center of Excellence, underscores the importance of understanding the complex interactions between immune cell types in diseases like MS. By targeting the metabolic abnormalities in B cells using BTK inhibitors, researchers hope to develop more effective and targeted therapies for MS that can mitigate inflammation and prevent disease progression.
