Therapeutic targeting of B cell-mediated adaptive immune responses to traumatic brain injury (TBI) (RPA Pilot / Seed Project)

Contusions are a common pathoanatomical type of traumatic brain injury (TBI), presenting as focal regions of tissue damage. Excitotoxicity and cytokine release trigger early neuroinflammation, followed by infiltration of myeloid cells. The dynamics and roles of innate immune cells have been extensively studied in TBI. Far less is known about the nature of the adaptive immune response. Studies in stroke and spinal cord injury suggest B cell-mediated adaptative immunity plays a significant role in the evolution of CNS injury. Clinically, autoantibodies to CNS antigens are detectable in serum after TBI, implicating peripheral B cell activation. However, evidence for B cell diapedesis into brain after TBI is woefully incomplete, and the potential role of B cells in modulating outcomes is unknown. We have preliminary data demonstrating delayed B cell diapedesis into the contused cortex. Further, our work suggests that B cells may aggregate into structures akin to germinal centers or ectopic lymphoid structures and may differentiate into antibody producing cells. These novel studies leverage the complementary TBI, stroke, and B cell neuroimmunology expertise of two experienced investigators to begin to unravel the role B cells play in brain after TBI and develop translationally relevant intervention strategies to promote beneficial B cell-mediated adaptive immune responses.