The BAFF/APRIL system as an inducer of B cell self-reactivity in spinal cord injury
Funded in: 2017, 2018, 2019, 2020
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Problem: B cells (lymphocytes) activation increase the secondary degenerative damage after SCI
Target: Cytokines (BAFF) involved in the activation of the B cells producing self reactive antibodies
Goal: block the activation of B cells as a therapeutic strategy for SCI by blocking the activation of B cells
B cells are immune cells that belong to the lymphocyte population. They recognize and bind antigens using a specific receptor, become activated and undergo maturation into effector plasma cells that produce large amounts of antibodies. Increasing evidence indicates that B cells are activated by spinal cord injury (SCI) and that they participate in consecutive degenerative damage to the central nervous system by production of pathologic self-reactive antibodies (antibodies directed against the body’s own tissue). It is still unknown how this antibody response is regulated, although preliminary results indicate the involvement of the cytokines B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL).
The project aims at identifying the prevalence of self-reactivity in SCI patients and at determining to what extent the BAFF/APRIL system is activated in SCI patients and correlates with the production of these self-reactive antibodies. How the BAFF/APRIL system contributes to antibody production and aberrant B cell functioning in SCI patients is addressed using an in vitro screening system. Finally, whether the BAFF/APRIL system enhances self-reactivity and whether its inhibition might have therapeutic value is examined in a mouse model for SCI.
The results of this project will resolve whether activation of the BAFF/APRIL system enhances pathologic self-reactivity in SCI pathology and whether blocking the system represents a new and powerful approach to treat SCI patients.