The multifaceted role of B cells in traumatic spinal cord injury: Antibody-dependent and antibody-independent mechanisms

Abstract

A traumatic spinal cord injury (SCI) is caused by an acute insult to the spinal cord that inflicts severe damage to the nerve tissue and leads to impaired motor, sensory, and autonomic functions. After the initial injury, a secondary injury phase occurs, which is characterized by an excessive inflammatory response mediated by resident and infiltrating peripheral immune cells that accumulate within the spinal cord lesion. Increasing evidence supports the involvement of B cells in this secondary injury phase post-SCI. Elevated B cell numbers have been reported following experimental SCI, both within and outside of the spinal cord, as well as in human post- mortem spinal cord tissue. In the injured spinal cord, B cells have been detected at different stages of maturation and have been shown to form ectopic follicle-like structures, indicating their functional relevance post-SCI. Furthermore, enhanced B cell differentiation into antibody-secreting cells has been observed, accompanied by increased (auto)antibody levels against various central nervous system proteins. Importantly, B cell depletion and knockout mouse studies have indicated that B cells could modulate other immune cells and contribute to impaired functional recovery after traumatic SCI, highlighting the potential of targeting B cell responses in the development of more specific and personalized therapeutic strategies for SCI patients. Hence, this review provides a comprehensive overview of recent advances in understanding the role of B cells in traumatic SCI, integrating findings from both animal and human studies.