B Cells: Key Players in Immune Responses and Potential for Multiple Sclerosis Prevention

A new category of medications, known as Bruton’s tyrosine kinase (BTK) inhibitors, may disrupt this abnormal B cell respiration.The Perelman School of Medicine at the University of Pennsylvania has conducted research that could potentially lead to the development of new treatments for multiple sclerosis (MS). This study, featured in Science Immunology, discovered that B cells play a crucial role in regulating myeloid cells, which can impact MS flare-ups. Dr. Amit Bar-Or, a professor of Neurology and director of Penn’s Center for Neuroinflammation and Neurotherapeutics, explained that this finding challenges the previous belief that T cells were the primary drivers of immune responses and the cause of MS. Instead, the research emphasizes the significance of interactions between different cell types.

Our understanding of the immune system has expanded to show that it plays a more active role than previously thought.

A well-functioning immune system is constantly regulating immune responses by either activating or suppressing them. It does this by releasing various cytokines, which communicate with other cell types to dictate their response. Typically, every immune response triggers a corresponding counter response, leading to a continuous cycle of regulation. This “push-me-pull-you” dynamic helps to maintain the proper balance between immune responses. As a result, an individual’s immune system is able to respond to infections while also preventing an overactive response that could harm the body, such as in the case of autoimmune diseases like MS.

By doing so, the immune system is able to effectively respond to stimuli while also preventing potential harm to the body.In a recent study, scientists utilized human samples and mouse models of MS to demonstrate that the communication of cytokines between B cells and T cells is disrupted in MS. They also discovered that the B cells of MS patients produce an abnormal cytokine profile that stimulates myeloid cells to create an inflammatory reaction. These findings are rooted in metabolic dysregulation within the B cells, specifically in a process called oxidative phosphorylation, a form of mitochondrial respiration. The researchers observed that healthy B cells can metabolize oxygen and release chemical energy signals that trigger a response in the B cells themselves.After that, it also affects myeloid cells, instructing them to generate either a pro- or anti-inflammatory reaction. However, when this B cell metabolism becomes too active, as it does in MS, the signaling leads to abnormal responses in both myeloid and T cells, which are linked to MS symptom flare-ups.

“A promising approach for new MS treatments could involve partially reducing respiration in B cells, which could in turn halt the chain of interactions between immune cells that causes inflammation and MS activity,” Bar-Or explained.

The researchers also demonstrated that a new category of medications, known as BTK inhibitors, achieves this effect. These drugs slow down the excessive activity of B cells, preventing the cascade of interactions between immune cells.BTK inhibitors have the ability to regulate B cell respiration and stabilize the activity of B cells in MS patients. This prevents the release of abnormal cytokines that contribute to pro-inflammatory responses from myeloid cells and T cells. Unlike existing MS treatments that deplete B cells, BTK inhibitors correct metabolic abnormalities without compromising the immune system’s ability to mount specific immune responses, such as producing antibodies in response to infections or vaccinations. This makes BTK inhibitors a promising alternative for MS patients.