The Role of B1 Cells in Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is recognized as one of the main causes of severe neurological disability. However, the mechanisms of secondary tissue damage still need to be clarified. The involvement of main populations of immune cells in the processes associated with TBI has been described in sufficient detail. However, the specific role of B1 lymphocytes has not been described in detail. This study investigates possible ability of B1 cells and their natural autoantibodies (NAA) to modulate the immune response during TBI. The research is based on the hypothesis that B1 cells could recognize neuronal lipid rafts (NLR) released from damaged neurons. It is assumed that this interaction helps to regulate the intensity of neuroinflammation and possibly stimulate regeneration. To test this concept in vivo, a mouse model of TBI was used to evaluate the neuroprotective effects of intraperitoneal NLR administration. Cognitive functions after treatment were assessed using Barnes-Maze behavioral test. In vitro experiments were conducted to evaluate the activation and proliferation of B1 lymphocytes after NLR stimulation. The main methods used in the study were flow cytometry, analysis of secreted immunoglobulins, assessment of gene expression for pro-inflammatory and anti-inflammatory markers in the brain after TBI, and histopathological examination of the damaged area. Our data suggest an important role of B1 cells in restoring the CNS microenvironment after injury. We found that NLR caused expansion of CD19+IgM+CD5+ B1a cells and production of IgM in vitro. Intraperitoneal administration of NLR significantly improved functional recovery for TBI and promoted brain tissue repair at the site of injury. It can be concluded that B1 lymphocytes act as one of the most important regulators of the neuroinflammatory response in TBI. The targeted use of B1 cells has great potential in the future to improve the effectiveness of the treatment of patients with severe forms of TBI.